PMID: 21167740

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

PMID: 35462462 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive

Case#:Table II, MPS-I, Enzyme activity=1.15

DiseaseAssertion: MPS1

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: 1.15 umol/hr/L blood (newborn blood spot)

CaseUrineGAGs:

CaseERT:

CaseBMT:

Variant1:c.246C>G (p.His82Gln)

Variant1ClinVarID: 92637

Variant1CAID: CA220506

Variant2: c.246C>G (p.His82Gln)

Variant2ClinVarID: 92637

Variant2CAID: CA220506

AdditionalVariants:

ParentalGenotype:

PreviouslyPublished

Case#:Table II, MPS-1, Enzyme activity=1.05

DiseaseAssertion: MPS1

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: 1.05 umol/hr/L blood, newborn blood spot

CaseUrineGAGs:

CaseERT:

CaseBMT:

Variant1:c.208C>T (p.Gln70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.208C>T (p.Gln70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants:

ParentalGenotype:

PreviouslyPublished

Case#: Patient 28, male, Han origin, 1 year 9 months old (age at diagnosis)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 1.1 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.710T>G (p.L237R)

Variant1ClinVarID: N/A

Variant1CAID: CA355962113

Variant2: c.973-4G>A

Variant2ClinVarID: 558027

Variant2CAID: CA2802154

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

This paper was listed under the ClinVar entry for this variant; however, only as an example to prove loss-of-function variants in IDUA are known to be pathogenic

Case#: Patient 6, male, Han origin, 13 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Macrocephaly (HP:0000256)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Global Developmental Delay, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 0.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.236C>T (p.A79V)

Variant1ClinVarID: 1458769

Variant1CAID: CA356987

Variant2: c.589G>A (p.G197S)

Variant2ClinVarID: 1526094

Variant2CAID: CA355961839

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 37, male, Han origin, age at diagnosis not available

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 1.5 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.2T>C (p.Met1Thr)

Variant1ClinVarID: 639529

Variant1CAID: CA2801095

Variant2: c.2T>C (p.Met1Thr)

Variant2ClinVarID: 639529

Variant2CAID: CA2801095

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed by parental testing.

PreviouslyPublished N/A

Case#: Patient 16, male, Han origin, 2.5 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 1.5 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.2T>C (p.M1?)

Variant1ClinVarID: 639529

Variant1CAID: CA2801095

Variant2: c.1593delG (p.Leu532CysfsTer28)

Variant2ClinVarID: N/A

Variant2CAID: CA2586965986

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 23, male, Han origin, 3.5 years old (age at diagnosis)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 3.5 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1-2C>G

Variant1ClinVarID: N/A

Variant1CAID: CA2586973510

Variant2: c.1189+5G>T

Variant2ClinVarID: N/A

Variant2CAID: CA2586965966

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 2, Han origin, male, 1 year and 3 months old (age at diagnosis)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia (HP:0001263, HP:0000256, HP:0001387, HP:0011369, HP:0001433, HP:0100790)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Airway obstruction (HP:0006536)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 1.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.159C>A (p.C53X)

Variant1ClinVarID: 1458768

Variant1CAID: CA355945972

Variant2: c.546G>C (p.E182D)

Variant2ClinVarID: 4069690

Variant2CAID: CA355961740

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 29, male, Han origin, 11 years old (age at diagnosis)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: Macrocephaly, Joint stiffness, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0000256, HP:0001387, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Global Developmental Delay, Mongolian macula (HP:0001263, HP:0011369)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 1.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1037T>G (p.L346R)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.1898C>T (p.S633L)

Variant2ClinVarID: 556406

Variant2CAID: CA355966010

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 35, female, Han origin, 3 years old (age at diagnosis)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Global Developmental Delay, Macrocephaly, Joint stiffness, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0001387, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: N/A

CaseNotHPOs: Mongolian macula (HP:0011369)

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 1.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1227dupG (paper says c.1225dupC but according to the variant sequence this should be c.1227dupG - a known variant)

Variant1ClinVarID: 929237

Variant1CAID: CA1139658406

Variant2: c.1244_1271del27 - Allele registry states that the range is off by 1, noting a deletion of 28 being found instead of 27.

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: 10, Male, 0.6 years (diagnosed), 7.8 years (report), 9.0 kg (weight), 74 cm (height), Iranian

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Parents are not consanguineous

CasePresentingHPOs: HP:0001249, HP:0001999, HP:0000943, HP:0001387, HP:0100790, HP:0000365, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Hernia, Deafness, Hydrocephalus)

CaseHPOFreeText: HM/HSM, Chronic Rhinorrhea

CaseNotHPOs: HP:0007957 (Corneal Capacity)

CaseNotHPOFreeText: Cardiac Manifestations

CaseEnzymeAssay: IDUA activity 2.08 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 7.8 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: p.G84R

Variant2: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: 12, Female, 0.9 years (diagnosed), 10.1 years (report), 26 kg (weight), 108 cm (height), Iranian

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Parents are consanguineous

CasePresentingHPOs: HP:0001999, HP:0100790 (Facial Dysmorphic Features, Hernia)

CaseHPOFreeText: HM/HSM

CaseNotHPOs: HP:0001249, HP:0000943, HP:0001387, HP:0000365, HP:0007957, HP:0000238 (Mental Retardation, Multiple Dysostosis, Joint Stiffness, Deafness, Corneal Opacity, Hydrocephalus)

CaseNotHPOFreeText: Chronic Rhinorrhea, Cardiac Manifestations

CaseEnzymeAssay: IDUA activity 1.01 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 7.4 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: p.Y109H

Variant2: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: 2, Male, 0.9 years (diagnosed), 4.2 years (report), 11 kg (weight), 65 cm (height), Iranian

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Parents are consanguineous

CasePresentingHPOs: HP:0000943, HP:0001387 (Multiple Dysostosis, Joint Stiffness)

CaseHPOFreeText: HM/HSM,

CaseNotHPOs: HP:0001249, HP:0001999, HP:0100790, HP:0000365, HP:0007957, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Hernia, Deafness, Corneal Opacity, Hydrocephalus)

CaseNotHPOFreeText: NM/HSM, Chronic Rhinorrhea, Cardiac Manifestations

CaseEnzymeAssay: IDUA activity 7.06 (μmol/spot.20h)

CaseUrineGAGs: Quantitative urinary GAG 14.22 (mg/gCr)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: p.S157P

Variant2: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient 2, Female, 1 years 6 months (diagnosed), 11 years (report), deceased, Tunis (Tunisian origin)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Parents are consanguineous between 2nd cousins

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Leukocyte IDUA activity 0.1% (% normal) ; determined in sonicated leukocyte pellets using the artificial substrate 4-methylumbellifery IDUA

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sequencing exons and intro-exon junctions; Phenol/chloroform procedure

Variant1: p.F177S

Variant1ClinVarID: N/A

Variant1CAID: CA355961706

Variant2: p.F177S

Variant2ClinVarID: N/A

Variant2CAID: CA355961706

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: T388R

Variant1ClinVarID: 496834

Variant1CAID: CA91169370

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: R492P

Variant1ClinVarID: 11918

Variant1CAID: CA256120

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: R89W

Variant1ClinVarID: 580286

Variant1CAID: CA2801156

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: G116R

Variant1ClinVarID: 712837

Variant1CAID: CA2801880

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: V454I

Variant1ClinVarID: 92630

Variant1CAID: CA145872

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: A75T

Variant1ClinVarID: 222993

Variant1CAID: CA356994

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: G51D

Variant1ClinVarID: 193061

Variant1CAID: CA274902

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: L346R

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: F188L

Variant1ClinVarID:

Variant1CAID: CA355961777

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: W306L

Variant1ClinVarID: 2203497

Variant1CAID: CA355962596

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: P533R

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: 2, Male, 4 years 4 months (diagnosed), 17 years (report), weight at presentation : NA, Height at presentation NA, Born in Uruguay

Disease Assertion: Hurler Scheie ( attenuated phenotype)

FamilyInfo: Parents are not consanguineous

Case Presenting HPOs: HP: 0002808, HP: 0002937, HP: 0000280, HP:0000470, HP:0001376, HP:0034337, HP: 0000768, HP:0000943 (Kyphosis, Hemivertebrae, Coarse face, Short neck, Limitation of joint mobility, claw hands, pectus carinatum, dysostosis multiplex )

CaseHPOFreeText: Bony dysplasia

CaseNotHPOs: HP:0007957 HP:0001249, HP:0001433, ( Corneal opacity , Intellectual disability , visceromegaly)

CaseNotHPOFreeText:

CaseEnzymeAssay: IDUA enzyme in dried blood spot 0.26 nmol/h/L ( 2.20-11.70 )

CaseUrineGAGs: NA CaseERT: N/A

CaseBMT: N/A

Genotyping Method: Sanger Sequencing

Variant1: p.L18P (c.53C>T)

Variant1ClinVarID: 193062

Variant1CAID: NA

Variant2: p.W402X

Variant2ClinVarID: 11908

Variant2CAID: 220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: 1, Male, 4 years 8 months (diagnosed), 24 years (report), weight at 50th percentile at presentation, Height at 25th percentile at presentation, Argentanian

Disease Assertion: Hurler Scheie / Scheie Syndrome ( attenuated phenotype)

FamilyInfo: Parents are not consanguineous

Case Presenting HPOs: HP:0002828, HP:0001387, HP: 0000473, HP:0000034, HP: 0002680 (Multiple Joint contractures, Joint Stiffness, Torticollos, hydrocele, J shaped sella turcica )

CaseHPOFreeText: primary enuresis

CaseNotHPOs: HP:0001249, HP:0001433, (Intellectual disability , visceromegaly)

CaseNotHPOFreeText: NA

CaseEnzymeAssay: NA

CaseUrineGAGs: NA CaseERT: N/A

CaseBMT: N/A

Genotyping Method: Sanger Sequencing

Variant1: p.L18P (c.53C>T)

Variant1ClinVarID: 193062

Variant1CAID: NA

Variant2: p.L18P

Variant2ClinVarID: 193062

Variant2CAID: NA

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: 3, Male, 4 years 8 months (diagnosed), 9 years (report), weight at presentation : NA, Height at presentation NA, Brought from Brazil

Disease Assertion: Hurler Scheie ( attenuated phenotype)

Family Info: Parents are consanguineous ( first cousins)

Case Presenting HPOs: HP:0001376, HP:0034337, HP:0000943 ( Limitation of joint mobility, claw hands, dysostosis multiplex )

CaseHPOFreeText: crooked fingers, bilateral carpal tunnel syndrome

CaseNotHPOs: HP: 0000280, HP:0100543 ( Coarse features, cognitive impairment )

CaseNotHPOFreeText:

CaseEnzymeAssay: IDUA enzyme in leukocytes 0.73 nmol/h/mg protein ( 32-56 )

CaseUrineGAGs: 188 ug /gm Creatinine ( Ref 67-124) CaseERT: Laronidase at 5yrs 3 months

CaseBMT: N/A

Genotyping Method: Sanger Sequencing

Variant1: p.L18P (c.53C>T)

Variant1ClinVarID: 193062

Variant1CAID: NA

Variant2: p.L18P (c.53C>T)

Variant2ClinVarID: 193062

Variant2CAID: NA

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: 4, Male, 1 year 2 months (diagnosed), 6 years (report), weight at presentation : NA, Height at presentation NA, Brought from Brazil

Disease Assertion: Hurler Scheie ( mild phenotype)

Family Info: Parents are consanguineous ( first cousins)

Case Presenting HPOs: HP:0002788, HP:0034337 (Recurrent upper respiratory tract infections, Claw hand deformity )

CaseHPOFreeText: curved bones both hands, sporadic pain in hands and feet, respiratory allergy

CaseNotHPOs: HP: 0003271, HP:0100543 ( Visceromegaly, cognitive impairment )

CaseNotHPOFreeText:

CaseEnzymeAssay: IDUA enzyme in leukocytes 0.61 nmol/h/mg protein ( 32-56 )

CaseUrineGAGs: 218 ug /gm Creatinine ( Ref 79-256) CaseERT: Laronidase at 24 months, urticariaafter 23 infusions, Desensitisation done

CaseBMT: N/A

Genotyping Method: Sanger Sequencing

Variant1: p.L18P (c.53C>T)

Variant1ClinVarID: 193062

Variant1CAID: NA

Variant2: p.L18P (c.53C>T)

Variant2ClinVarID: 193062

Variant2CAID: NA

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient IV, origin of proband is Pakistani/Norway, male (hinted that proband is male in figure 1 caption)

DiseaseAssertion: Hurler syndrome (H)

FamilyInfo: No family information provided, but genotype information is provided (see ParentalGenotype)

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: 0.00 umol/mghour IDUA enzyme activity in patient IV. Reference range is 0.14 - 0.35 umol/mghour

CaseUrineGAGs: Information not stated in this paper

CaseERT: Don't know

CaseBMT: Don't know

Variant1: c.1469T>C, p.L490P

Variant1ClinVarID: 11919

Variant1CAID: CA220503

Variant2: c.(1828 + 1_1829‐1)(*1963?)del

Variant2ClinVarID: Not sure how to look up in CAR

Variant2CAID: Not sure how to look up in CAR

AdditionalVariants: No additional variants mentioned.

ParentalGenotype: Figure 1 has parental genotype information for this proband. It is stated that there is a "hereozygous presence" of an IDUA variant in DNA of patient IV's mother. It is suggested that patient IV inherited a pathogenic variant from his mother. The father of patient IV "carries a benign single nucleotide variant rs115929690 suggesting that patient IV has inherited... a benign variant from his father"

PreviouslyPublished: I do not believe this proband was previously published. The paper states that variant "c.1469T>C have been found in patients previously." It does not link the variant to a specific paper but instead references a list of papers. Here are the PMIDs of those paper: 7951228, 1301196, 1301941, and 7550232

Case#: Patient V, origin of proband is United Kingdom

DiseaseAssertion: Hurler syndrome (H)

FamilyInfo: No family information is provided

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: IDUA enzyme activity for this proband is N/A. The reference range is also N/A.

CaseUrineGAGs: Information not stated in this paper

CaseERT: Don't know

CaseBMT: Don't know

Variant1: c.1598C>G, p.P533R

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: c.(157 + 1_158‐1)_(1727 + 1_1728‐1)dup

Variant2ClinVarID: Not sure how to look up in CAR

Variant2CAID: Not sure how to look up in CAR

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental genotype information provided

PreviouslyPublished: I do not believe this proband was previously published. The paper states that variant "c.1598C>G have been found in patients previously." It does not link the variant to a specific paper but instead references a list of papers. Here are the PMIDs of those paper: 7951228, 1301196, 1301941, and 7550232

Case#: Patient 296, female, northern European origin, 8 months (age of diagnosis), 4 years and 9 months (age of death)

DiseaseAssertion: MPS1-H, severe

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: N/A

Variant2: c.1614del (delG1702)

Variant2ClinVarID: 167191

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2474, male, northern European origin, he was class valedictorian in high school and then a practicing attorney until his intellect deteriorated later in life.

DiseaseAssertion: MPS1-S, mild

FamilyInfo: Affected sister with MPS-1 who had a similar or slightly more severe clinical phenotype.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Fibroblasts has enabled detection of 0.041 ± 0.008 (n = 6) ng of IDUA protein of total cellular protein/mg (0.13% of normal mean). This gives a calculated specific activity and VmX, of 88 and 102 pmol/min/ng of IDUA toward the fluorogenic and heparin-derived disaccharide substrates, respectively, both of which are in the normal range.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.590-7G>A (678-7G>A)

Variant1ClinVarID: 222996

Variant1CAID: N/A

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: No additional case information provided

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.1 umol/g hr, reference range 10–50 umol/g hr.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.386-1G>A

Variant1ClinVarID: 1458772

Variant1CAID: CA355961254

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

1 individual from "other regions" was reported to have this variant in a cohort of 291 people with MPS1.

CAID: CA355961907

Genotype: NM_000203.3 c.606C>A p.(Tyr202Ter)

HPOFreeText: Phenotype: unknown

GenotypingMethod: bidirectional Sanger sequencing of the IDUA gene. IDUA exons and adjacent intron regions were amplified by PCR reactions and then sequenced

SupplementalInfo: Supplemental table S1

Mentioned that this variant has been seen in a previous publication: Matte (2003), but it doesn't sound like it's the same individual

Case#: No additional case information provided

DiseaseAssertion: MPSI-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.4 umol/g hr, reference range 10–50 umol/g hr.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1871A>T (p.D624V)

Variant1ClinVarID: N/A

Variant1CAID: CA355965955

Variant2: c.17_24dupCCCGCGCC (p.A9PfsTer102)

Variant2ClinVarID: N/A

Variant2CAID: CA645372294

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: No additional case information provided

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.09 umol/g hr, reference range 10–50 umol/g hr.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1278_1284dupCCCCCAG (p.G429PfsTer82)

Variant1ClinVarID: N/A

Variant1CAID: CA645372299

Variant2: c.208C>T (p.Q70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common a-L-iduronidase mutations (W402X and Q70X) among European patients

PMID: 7951228

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: YS of sibship 2, female, birth (age at diagnosis), 0.4 years old (age at ERT enrollment), 9.6 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Affected male OS (OS of sibship 2)

CasePresentingHPOs: HP:0000943, HP:0002828 (dysostosis, joint contractures)

CaseHPOFreeText: Mild to severe cardiac disease, mild organomegaly, mild progression of musculoskeletal symptoms

CaseNotHPOs: HP:0007957 (Corneal opacity)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay:

CaseUrineGAGs: N/A

CaseERT: Yes - After 10 years of ERT, cardiac symptoms showed some improvement into the mild to moderate range, organomegaly stabilized, and development remained normal.

CaseBMT: N/A

Variant1: c.1598C>G (p.P533R)

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: c.1598C>G (p.P533R)

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: OS of sibship 9, female, 7 years old (age at diagnosis), 14 years old (age at ERT enrollment), 7 years (duration of ERT)

DiseaseAssertion: MPS1-HS

FamilyInfo: Affected YS (YS of sibship 9)

CasePresentingHPOs: HP:0007957, HP:0000943, HP:0002828 (Corneal opacity, dysostosis, joint contracture)

CaseHPOFreeText: Cardiac disease, ocular, respiratory, and musculoskeletal involvement.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - At T2, ocular and cardiac symptoms progressed from mild to moderate/severe. In addition, pulmonary function worsened, and contractures and lower extremity weakness progressed. Had stabilization of dysostosis multiplex and no progression of motor function delays.

CaseBMT: N/A

Variant1: N/A

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 3, Turkish

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.494-1G>A

Variant1ClinVarID: 557942

Variant1CAID: CA355961634

Variant2: c.494-1G>A

Variant2ClinVarID: 557942

Variant2CAID: CA355961634

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 7, Turkish

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#:Patient Sample unique ID 52, Infant screened positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

DiseaseAssertion:None

FamilyInfo:None

CasePresentingHPOs:None

CaseHPOFreeText:None

CaseNotHPOs:None

CaseNotHPOFreeText: Normal examination at follow up after screening positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

CaseEnzymeAssay: IDUA activity 0.433 (5.2) umol/L/h (%DMA) during new born screening through dried blood spot (plasma) and 6.5 pmol/punch/h Confirmatory IDUA enzyme

CaseUrineGAGs: DS 3.2 g/mol creatinine and HS 2.6 g/mol creatinine (Normal)

CaseERT:No

CaseBMT:No

Variant1:heterozygous PD: c.235G>A; p.A79T (Normal examination)

Variant1ClinVarID:41682

Variant1CAID:CA000358

Variant2:heterozygous PD: c.667G>A; p.D223N

Variant2ClinVarID:2220838

Variant2CAID:CA363422841

AdditionalVariants: None

ParentalGenotype:None provided

PreviouslyPublished:N/A

Case#:Patient Sample unique ID 27, Infant screened positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

DiseaseAssertion:None

FamilyInfo:None

CasePresentingHPOs:None

CaseHPOFreeText:None

CaseNotHPOs:None

CaseNotHPOFreeText: Normal examination at follow up after screening positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

CaseEnzymeAssay: IDUA activity 0.351 (4.3) umol/L/h (%DMA) during new born screening through dried blood spot (plasma) and 10 pmol/punch/h Confirmatory IDUA enzyme

CaseUrineGAGs: DS 4.5 g/mol creatinine and HS 2.9 g/mol creatinine (Normal)

CaseERT:No

CaseBMT:No

Variant1:homozygous PD: c.235G>A; p.A79T (Normal examination)

Variant1ClinVarID:41682

Variant1CAID: CA000358

Variant2: homozygous PD: c.296C>T; p.T99I

Variant2ClinVarID:53610

Variant2CAID:CA326991

AdditionalVariants:None

ParentalGenotype:None provided

PreviouslyPublished:N/A

Case#:Patient Sample unique ID 29, Infant screened positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

DiseaseAssertion:None

FamilyInfo:None

CasePresentingHPOs:None

CaseHPOFreeText:None

CaseNotHPOs:None

CaseNotHPOFreeText: Normal examination at follow up after screening positive at birth (specimens with activity ≤15% of the DMA for enzyme activity and a CLIR screening algorithm result of indeterminate or MPS I)

CaseEnzymeAssay: IDUA activity 0.623 (7.5) umol/L/h (%DMA) during new born screening through dried blood spot (plasma) and 11.1 pmol/punch/h Confirmatory IDUA enzyme

CaseUrineGAGs: DS 3.1 g/mol creatinine and HS 2.4 g/mol creatinine (Normal)

CaseERT:No

CaseBMT:No

Variant1:heterozygous VUS: c.787A>T; p.R263W (Normal examination)

Variant1ClinVarID:2664494

Variant1CAID:CA411263334

Variant2: heterozygous PD: c.246C>G; p.H82Q

Variant2ClinVarID:92637

Variant2CAID:CA220506

AdditionalVariants:None

ParentalGenotype:None provided

PreviouslyPublished:N/A

Case#: P3, Female, 15.7 years (diagnosed), 22.6 (report), 27 kg (weight), 128 cm (height), Algerian

DiseaseAssertion: Scheie Syndrome

FamilyInfo: Parents are consanguineous

CasePresentingHPOs: HP:0001999, HP:0000943, HP:0002240, HP:0001387, HP:0007957, HP:0000238 (Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Hernia(Ombelical), Corneal Opacity, Hydrocephalus)

CaseHPOFreeText: Chronic Rhinorrhea, Cardiac Manifestations(Mitral Insufficiency & Aortic Insufficiency)

CaseNotHPOs: HP:0001249, (Mental Retardation)

CaseNotHPOFreeText: HM/HSM

CaseEnzymeAssay: IDUA Enzyme activity 6 (% to the reference range mean)

CaseUrineGAGs: GAG quantitation 95 (fold change to the reference range mean according to age)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Direct DNA Fragments Sequencing

Variant1: c.1598C>G (p.Pro533Arg)

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: c.1598C>G (p.Pro533Arg)

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: P9, Female, 8.3 years (diagnosed), 14.9 (report), 35 kg (weight), 135 cm (height), Algerian

DiseaseAssertion: Scheie Syndrome

FamilyInfo: Parents are not consanguineous

CasePresentingHPOs: HP:0001999, HP:0000943, HP:0001433, HP:0100790, HP:0000365, HP:0000238 (Facial Dysmorphic Features, Multiple Dysostosis, Hepatosplenomegaly, Hernia(Ombelical), Deafness(mixed), Hydrocephalus)

CaseHPOFreeText: Cardiac Manifestations(Mitral Insufficiency & Aortic Insufficiency)

CaseNotHPOs: HP:0001249, HP:0001387, HP:0007957 (Mental Retardation, Joint Stiffness, Corneal Opacity)

CaseNotHPOFreeText: Chronic Rhinorrhea

CaseEnzymeAssay: IDUA Enzyme activity 0 (% to the reference range mean)

CaseUrineGAGs: GAG quantitation 23 (fold change to the reference range mean according to age)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Direct DNA Fragments Sequencing

Variant1: c.1598C>G (p.Pro533Arg)

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: c.1598C>G (p.Pro533Arg)

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: One patient from Norway

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.152G>A (p.G51D)

Variant1ClinVarID: 193061

Variant1CAID: CA274902

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: One patient from Egypt

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguinity present in the family

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.682insAC in paper but correct nomenclature is c.594_595insAC (p.Leu199ThrfsTer2)

Variant1ClinVarID: N/A

Variant1CAID: CA2586973525

Variant2: c.682insAC in paper but correct nomenclature is c.594_595insAC (p.Leu199ThrfsTer2)

Variant2ClinVarID: N/A

Variant2CAID: CA2586973525

AdditionalVariants: c.346G>A (p.G116R)

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 1, female, 7.3 months (age at diagnosis), 14.1 months (age at HSCT), 7 MRI + neuropsychological observations over the course of 17 years.

DiseaseAssertion: MPS-1H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 52.6 nmol/h/mg (Normal values: 11-43 nmol/h/mg)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Yes

Variant1: c.159C>A (p.C53X)

Variant1ClinVarID: 1458768

Variant1CAID: CA355945972

Variant2: c.653T>C (p.L218P)

Variant2ClinVarID: 222995

Variant2CAID: CA356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 9, female, 7.9 months (age at diagnosis), 12.0 months (age at HSCT), 9.5 - 12.7 months (age at ERT), 4 MRI + neuropsychological observations over the course of 7 years.

DiseaseAssertion: MPS-1H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 24.8 nmol/h/mg (Normal values: 11-43 nmol/h/mg)

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: Yes, transplanted with an unrelated cord blood unit.

Variant1: c.1487C>G (p.P496R)

Variant1ClinVarID: 496861

Variant1CAID: CA2802275

Variant2: c.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient W2, 10 years old, Chinese. The patient had normal intelligence based on their performance in school.

DiseaseAssertion: MPS1-H/S

FamilyInfo: Maternal and paternal DNA were interpreted.

CasePresentingHPOs: Short stature, coarse facial features, severe skeletal deformities (HP:0004322, HP:0000280, HP:0000924)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1091C>T (p.T364M)

Variant1ClinVarID: 11925

Variant1CAID: CA256126

Variant2: c.1091C>T (p.T364M)

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 6, born in 2003 (paper published in 2017), 1 year (age at first treatment), 20 months (age at last treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 31 ng/mol (31 weight matched enzyme reference assay)

CaseUrineGAGs: 0.39 DS/CS

CaseERT: Yes

CaseBMT: Yes, MUD

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.208C>T (p.Q70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 4, born in 1996 (paper published in 2017), 10 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding, retinopathy (HP:0007957, HP:0000488)

CaseHPOFreeText: N/A

CaseNotHPOs: Cataract (HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 32.77 ng/mol (46.19 weight matched enzyme reference assay)

CaseUrineGAGs: 1.08 DS/CS

CaseERT: No

CaseBMT: Yes, Sib

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 25, born in 2005 (paper published in 2017), 20 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Cataract, retinopathy (HP:0000518, HP:0000488)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 43 ng/mol (28 weight matched enzyme reference assay)

CaseUrineGAGs: 0.45 DS/CS

CaseERT: Yes

CaseBMT: Yes, Cord

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.386-1G>A

Variant2ClinVarID: 1458772

Variant2CAID: CA355961254

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 18, born in 2012 (paper published in 2017), 7 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 79.39 ng/mol (42.66 weight matched enzyme reference assay)

CaseUrineGAGs: 0.51 DS/CS

CaseERT: Yes

CaseBMT: Yes, Uncle

Variant1: c.1045G>T (p.D349Y)

Variant1ClinVarID: 638075

Variant1CAID: CA355963146

Variant2: c.1045G>T (p.D349Y)

Variant2ClinVarID: 638075

Variant2CAID: CA355963146

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 20, born in 2003 (paper published in 2017), 20 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 57.2 ng/mol (26 weight matched enzyme reference assay)

CaseUrineGAGs: 0.63 DS/CS

CaseERT: No

CaseBMT: Yes, Cord

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1898C>A (p.S633X)

Variant2ClinVarID: 1068474

Variant2CAID: CA355966009

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient No. 6 (Table 1), White race, male, 2.13 years old (age at time of gene therapy), 85 IQ score, 1.96 years since gene therapy (1.5 years since latest visit)

DiseaseAssertion: MPS-IH

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Yes

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.979G>C (p.A327P)

Variant2ClinVarID: 167190

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 5, 9 years old, Iranian

DiseaseAssertion: MPS1-H/S (Intermediate)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity not detected

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1A>C (p.M1L)

Variant1ClinVarID: 550458

Variant1CAID: CA355945204

Variant2: c.1A>C (p.M1L)

Variant2ClinVarID: 550458

Variant2CAID: CA355945204

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 31298590

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 4, 11 years old, Iranian

DiseaseAssertion: MPS1-H (Severe)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity not detected

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1029C>A (p.Y343X)

Variant1ClinVarID: 222997

Variant1CAID: CA356984

Variant2: c.1029C>A (p.Y343X)

Variant2ClinVarID: 222997

Variant2CAID: CA356984

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Male, 7 years old (age of onset), 34 years old (age at report), Venezuelan

DiseaseAssertion: MPS1-S

FamilyInfo: First son of a healthy non-consanguineous parents; unremarkable family history

CasePresentingHPOs: Joint stiffness, claw hand deformity, muscle weakness, myalgia, arthralgia, blurred vision, corneal clouding, umbilical hernia, coarse facial features, prominent forehead, synophrys, anteverted nose, bulbous nose, short columella, thick lips, short neck, thick skin (HP:0001387, HP:0034337, HP:0001324, HP:0003326, HP:0002829, HP:0000622, HP:0007957, HP:0001537, HP:0000256, HP:0011220, HP:0000664, HP:0000463, HP:0000414, HP:0002000,HP:0000219, HP:0000470, HP:0001072)

CaseHPOFreeText: Frequent falls and at 26 years old his weight was 51.5 kg (3rd percentile), height of 159 cm (<3rd percentile), head circumference of 57 cm (30-75th percentile). He had down-slating palpebral fissures, a symmetric chest and his abdomen was without organomegaly. He had limited joint movements of the upper limbs as well. His mental development was normal.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Decreased activity of alpa-L-iduronidase in leukocytes: 0.01 nmol/min/mg (reference value 0.31 to 0.71 nmol/min/mg. Dried blood spot on filter paper: 0.8 umol/l/h (reference value >2.5 umol/lh).

CaseUrineGAGs: Electrophoretic urinary GAGs showed one band corresponding to the migration of dermatan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1190-1delG

Variant1ClinVarID: 2734639

Variant1CAID: CA2586965967

Variant2: c.1708G>C (p.D570H)

Variant2ClinVarID: 551300

Variant2CAID: CA355965252

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 38, 3 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0100790)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.2% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1373T>C (p.Leu458Pro)

Variant1ClinVarID: N/A

Variant1CAID: CA355964255

Variant2: c.1373T>C (p.Leu458Pro)

Variant2ClinVarID: N/A

Variant2CAID: CA355964255

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 15, 5 months old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, recurrent infections (HP:0000280, HP:0001433, HP:0002719)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.3% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.568_581del (p.Asn190Hisfs*204)

Variant1ClinVarID: 3639714

Variant1CAID: CA2801994

Variant2: c.568_581del (p.Asn190Hisfs*204)

Variant2ClinVarID: 3639714

Variant2CAID: CA2801994

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 26, 4 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, intellectual disability, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0001249, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.3% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1255G>C (p.Gly419Arg)

Variant1ClinVarID: N/A

Variant1CAID: CA355963703

Variant2: c.1255G>C (p.Gly419Arg)

Variant2ClinVarID: N/A

Variant2CAID: CA355963703

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 44, 5 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.0% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1874A>G (p.Tyr625Cys)

Variant1ClinVarID: 100723

Variant1CAID: CA267584

Variant2: c.1874A>G (p.Tyr625Cys)

Variant2ClinVarID: 100723

Variant2CAID: CA267584

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 29, 1 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding (HP:0000280, HP:0001433, HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.6% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1339delC (p.Arg447Alafs*10)

Variant1ClinVarID: N/A

Variant1CAID: CA2586965980

Variant2: c.1339delC (p.Arg447Alafs*10)

Variant2ClinVarID: N/A

Variant2CAID: CA2586965980

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 35, 3 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0100790)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.2% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1373T>C (p.Leu458Pro)

Variant1ClinVarID: N/A

Variant1CAID: CA355964255

Variant2: c.1373T>C (p.Leu458Pro)

Variant2ClinVarID: N/A

Variant2CAID: CA355964255

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 57, 6 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.9% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.895G>T (p.Glu200Ter)

Variant1ClinVarID: 987878

Variant1CAID: CA355962511

Variant2: c.1960T>A (p.Ter654Arg)

Variant2ClinVarID: N/A

Variant2CAID: CA355966128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 45, 10 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, joint contractures, corneal clouding, recurrent infections, intellectual disability (HP:0000280, HP:0002828, HP:0007957, HP:0002719, HP:0001249)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.0% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1898C>T (p.Ser633Leu)

Variant1ClinVarID: 556406

Variant1CAID: CA355966010

Variant2: c.1898C>T (p.Ser633Leu)

Variant2ClinVarID: 556406

Variant2CAID: CA355966010

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 32, 3 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: Sibling of Patient 31

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.5% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1373T>C (p.Leu458Pro)

Variant1ClinVarID: N/A

Variant1CAID: CA355964255

Variant2: c.1373T>C (p.Leu458Pro)

Variant2ClinVarID: N/A

Variant2CAID: CA355964255

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 20, 2 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, intellectual disability (HP:0000280, HP:0001433, HP:0001249)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 4.0% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.793-1G>A

Variant1ClinVarID: 557472

Variant1CAID: CA2802097

Variant2: c.793-1G>A

Variant2ClinVarID: 557472

Variant2CAID: CA2802097

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 9, 11 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0100790)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 4.5% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.523_534del (p.Trp175_Glu178del)

Variant1ClinVarID: 2734635

Variant1CAID: CA645372297

Variant2: c.523_534del (p.Trp175_Glu178del)

Variant2ClinVarID: 2734635

Variant2CAID: CA645372297

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 24, 1 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, joint contractures, corneal clouding, dysostosis multiplex, intellectual disability (HP:0000280, HP:0002828, HP:0007957, HP:0000943, HP:0001249)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.7% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1096_1099del (p.Thr366Argfs*73)

Variant1ClinVarID: 1065522

Variant1CAID: CA2499217017

Variant2: c.1096_1099del (p.Thr366Argfs*73)

Variant2ClinVarID: 1065522

Variant2CAID: CA2499217017

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 4, Male, 3 months (onset), 5 months (diagnosed), 8 months (report), deceased (at 2y)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0000256, HP:0002240, HP:0001744, HP:0000280, HP:0000943, HP:0007957 Macrocephaly (progressive hydrocephalus since 3m), Hepatomegaly (moderate), Splenomegaly (mild), Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (delayed since 3m), Quadruhyperreflexy (at 8m)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: p.A327P

Variant2ClinVarID: 167190

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 13, Female, Infancy (onset), 1,5 years (diagnosed), 5 years (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0001387, HP:0002240, HP:0001744, HP:0012185, HP:0000280, HP:0000943, HP:0007957 (Joint Stiffness, Hepatomegaly, Splenomegaly, Carpal Tunnel Syndrome, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Delayed)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1650+5G>A (splicing error)

Variant2ClinVarID: 92634

Variant2CAID: CA220504

AdditionalVariants: p.Q33H, p.R105Q, p.N181, p.A314, p.T410, p.V454I, p.R489

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 15, Female, Infancy (onset), 10 months (diagnosed), 12 years (report)

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0004322, HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0000023, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Macrocephaly, Joint Stiffness, Hepatomegaly (moderate), Splenomegaly (moderate), Inguinal Hernia, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (Delayed), Systolic murmur 3-4/6, After ERT: decreased illness (obstructive bronchitis), decreased organomegaly, increased mobility)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: Decreased excretion of GAGs in the urine

CaseERT: Had an ERT

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.R628X

Variant2ClinVarID: 550421

Variant2CAID: CA2802462

AdditionalVariants: p.A8, p.A20, p.Q33H, p.L118

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 3, Female, 6 months (onset), 13 months (diagnosed), 14 months (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0002240, HP:0001744, HP:0000280, HP:0000943, HP:0007957 (Hepatomegaly (moderate), Splenomegaly (mild), Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Developmental quotient 92 in 13m), Hyperechogenic mitral valve (with insufficiency of 1st-2nd grade)

CaseNotHPOs: HP:0004322, HP:0000256, HP:0001387 (Short Stature, Macrocephaly, Joint Stiffness)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation (performed in March 2008)

GenotypingMethod: Not Provided

Variant1: p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: p.W402X

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 10, Male, 2 months (onset), 2 months (diagnosed), 2 months (report), deceased (due to severe graft versus host disease)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0002240, HP:0001744, HP:0001537, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Hepatomegaly (moderate), Splenomegaly (moderate), Umbilical Hernia, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Delayed since early infancy)

CaseNotHPOs: HP:0000256 (Macrocephaly)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation at 5m

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.Q70X

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: p.Q33H/Q33H, p.L118/L118

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 13, female, 8 months (age at presentation).

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguinity in the family not present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, dystosis multiplex, hepatomegaly, joint stiffness, intellectual disability, splenomegaly (HP:0007957, HP:0000256, HP:0000943, HP:0002240, HP:0001387, HP:0010864, HP:0001744)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.783delC (p.His262Thrfs*55)

Variant1ClinVarID: 956890

Variant1CAID: CA2802083

Variant2: c.783delC (p.His262Thrfs*55)

Variant2ClinVarID: 956890

Variant2CAID: CA2802083

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 23, male, 2 years (age at presentation).

DiseaseAssertion: MPS1-H/S

FamilyInfo: Consanguinity in the family not present for this patient. There was a prenatal diagnosis "CVS-carrier for p.M504R"

CasePresentingHPOs: Corneal clouding, coarse facial features, dystosis multiplex, hepatomegaly, joint stiffness, motor delay, splenomegaly, short stature (HP:0007957, HP:0000256, HP:0000943, HP:0002240, HP:0001387, HP:0001270, HP:0001744, HP:0004322)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1511T>G (p.M504R)

Variant1ClinVarID: N/A

Variant1CAID: CA355964770

Variant2: c.1524+1G>C

Variant2ClinVarID: 3653693

Variant2CAID: CA355964828

AdditionalVariants: N/A

ParentalGenotype: Father is a carrier for p.M504R and mother is a carrier for c.1524+1G>C

PreviouslyPublished N/A

Case#: Patient 2, female, 6 years (age at presentation)

DiseaseAssertion: MPS1-H/S

FamilyInfo: Consanguinity in the family present for this patient.

CasePresentingHPOs: Corneal clouding, dysostosis multiplex, hepatomegaly, joint contractures, splenomegaly (HP:0007957, HP:0000943, HP:0002240, HP:0100790, HP:0001744)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.223G>C (p.A75P)

Variant1ClinVarID: N/A

Variant1CAID: CA355946364

Variant2: c.223G>C (p.A75P)

Variant2ClinVarID: N/A

Variant2CAID: CA355946364

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 27, female, 1 year 6 months (age at presentation).

DiseaseAssertion: MPS1-H/S

FamilyInfo: Consanguinity in the family present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, dysostosis multiplex, hepatomegaly, inguinal hernia, joint stiffness, sleep disturbances, splenomegaly, umbilical hernia (HP:0007957, HP:0000256, HP:0000943, HP:0002240, HP:0000023, HP:0001387, HP:0002360, HP:0001744, HP:0001537)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1855C>T (p.R619X)

Variant1ClinVarID: 280976

Variant1CAID: CA2802455

Variant2: c.1855C>T (p.R619X)

Variant2ClinVarID: 280976

Variant2CAID: CA2802455

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 25, UK

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 30, UK

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: The Scheie phenotype is characterized by aortic valve disease, corneal clouding, limited skeletal problems, but no mental retardation. This is a general assessment and not specific to this patient.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.590-7G>A; c.678-7G>A in the paper (old nomenclature)

Variant1ClinVarID: 222996

Variant1CAID: CA356990

Variant2: c.1198C>T (p.Q400X)

Variant2ClinVarID: 1683229

Variant2CAID: CA355963534

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 17, Cyprus

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: The paper states that "Hurler form is characterized by skeletal abnormalities, hepatosplenomegaly and severe mental retardation" but is not specific to this patient.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.659delG; c.747delG in the paper (old nomenclature)

Variant1ClinVarID: N/A

Variant1CAID: CA2802045

Variant2: c.659delG; c.747delG in the paper (old nomenclature)

Variant2ClinVarID: N/A

Variant2CAID: CA2802045

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 20, UK

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: The paper states that "Hurler form is characterized by skeletal abnormalities, hepatosplenomegaly and severe mental retardation" but is not specific to this patient.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.65delC; c.153delC in the paper (old nomenclature)

Variant2ClinVarID: 929238

Variant2CAID: CA437911597

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 8 (see Table 1), male, 10 years old (age at report), 1 year and 6 months (age of onset), height of 115 cm, weight of 19 kg, located in Tunis: Industrial region

DiseaseAssertion: MPS1 - intermediate

FamilyInfo: Parents were 3rd cousins (see Table 2), aged 34 yrs (M) and 40 yrs (F).

CasePresentingHPOs: HP:0004322, HP:0001999, HP:0000924 (Short stature, facial dysmorphia, skeletal abnormalities)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 0.050 μKat/kg

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1598C>G (p.P533R)

Variant1ClinVarID: 11910

Variant1CAID: CA:256112

Variant2: c.1598C>G (p.P533R)

Variant2ClinVarID: 11910

Variant2CAID: CA:256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2 (see Table 1), 1 year and 3 months - deceased (age at report), 1 month and a half (age at onset), male, height of 71 cm, weight of 12 kg, located in the Sfax: Industrial region.

DiseaseAssertion: MPS1 - severe

FamilyInfo: Two affected siblings (Patients 1 and Patient 3), three other familial relations (deceased), parents were 3rd cousins (see Table 2) aged 38 yrs (M) and 40 yrs (F).

CasePresentingHPOs: HP:0000280, HP:0002194, HP:0000238, HP:0000365, HP:0000023 (Coarse facial features, developmental delay, hydrocephaly, hearing impairment, inguinal hernia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: (p.F602X)

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: (p.F602X)

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID:33572941

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

PMID: 8213840

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 14, Italy

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.152G>A (p.G51D)

Variant1ClinVarID: 193061

Variant1CAID: CA274902

Variant2: c.1333_1335del (p.Asp445del)

Variant2ClinVarID: 840115

Variant2CAID: CA916082626

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 89, Turkey

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguineous parents

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.826_828del (p.Glu276del)

Variant1ClinVarID: 2734638

Variant1CAID: CA2586965949

Variant2: c.826_828del (p.Glu276del)

Variant2ClinVarID: 2734638

Variant2CAID: CA2586965949

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A