Case#: Patient No. 4 (Table 1), White race, male, 1.21 years old (age at time of gene therapy), 95 IQ score, 2.07 years since gene therapy (2 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.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#: Three patients are from The Netherlands

DiseaseAssertion: MPSI-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.653T>C (p.L218P)

Variant1ClinVarID: 222995

Variant1CAID: CA356986

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Three patients are from The Netherlands

DiseaseAssertion: MPSI-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.653T>C (p.L218P)

Variant1ClinVarID: 222995

Variant1CAID: CA356986

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 35 (Table 3)

DiseaseAssertion: Attenuated naïve MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 7 nmol/h/mg per DBS (dried blood spots) determined during NBS. 7.2 DBS protein concentration determined by Immuno-SRM (pmol/L).

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.299+5G>T

Variant2ClinVarID: N/A

Variant2CAID: CA549149418

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 35, Italy

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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.398_403del (p.Met133_Gly134del)

Variant2ClinVarID: 863830

Variant2CAID: CA2801912

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Three patients are from The Netherlands

DiseaseAssertion: MPSI-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.653T>C (p.L218P)

Variant1ClinVarID: 222995

Variant1CAID: CA356986

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 6, female, 8.3 months (age at diagnosis), 12.4 months (age at HSCT), 9.0 - 14.7 months (age at ERT), 5 MRI + neuropsychological observations over the course of 10 years.

DiseaseAssertion: MPS-1H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 32.7 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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 12 in Group 2 (patients who were at least 3 years of age at the time of introduction of ERT), 5 years old (age of diagnosis), 15 years old (baseline age), 19 years old (current age), male, Polish

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Anthropometric features

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Diagnosis of MPS I confirmed by the biochemical determination of α-l-iduronidase deficiency in leukocytes

CaseUrineGAGs: Baseline urinary GAG values ranged from 450 to 1330 mg/g of creatinine. For treated patients the reductions of urinary GAG ranged from 30% to 80% with a mean reduction of 55%, but it never approached the normal range for age.

CaseERT: Yes - for 208 weeks he received weekly intravenous infusions of 100 U/kg (0.58 mg/kg) laronidase

CaseBMT: No

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.793G>C (p.G265R)

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 24, born in 2009 (paper published in 2017), 8 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: 48.88 ng/mol (48.75 weight matched enzyme reference assay)

CaseUrineGAGs: 0.28 DS/CS

CaseERT: Yes

CaseBMT: Yes, MUD

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2, female, 18 months (age at diagnosis), 22 months (age at HSCT), weight of 12.1 kg (at HSCT), 5 years (age at report). Neurological development is not impaired.

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, kyphosis, abdominal distension, mild mitral regurgitation (HP:0000256, HP:0002808, HP:0003270, HP:0001653)

CaseHPOFreeText: Chronic hydrocephalus-VP-shunt

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Activity of alpha-L-iduronidase in leukocytes was normal from 5 months after cessation of ERT.

CaseUrineGAGs: Patient had normal excretion of total urine GAGs - but a small fraction of dermatansulfate remained detectable upon electrophoresis of total urinary GAGs.

CaseERT: Yes - 13 weeks of ERT before HSCT. Continued until day 50 of HSCT.

CaseBMT: Yes - interval diagnosis for HSCT (15 weeks). The donor was female and unrelated.

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1631_1640del

Variant2ClinVarID: N/A

Variant2CAID: CA1433071867

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 9, 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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.540_544del (p.W180X); c.628del5 in the paper

Variant2ClinVarID: 3775043

Variant2CAID: CA2573332240

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 22-month-old Norwegian female patient

DiseaseAssertion: MPS-H

FamilyInfo: Mother and father received parental testing.

CasePresentingHPOs: Joint stiffness (HP:0001387)

CaseHPOFreeText: She had a tendency to fall without normal protective reactions. Typical facial appearance and other clinical findings were suggestive of MPS I Hurler, and this diagnosis was also supported by X-ray images which showed characteristic skeletal changes. Motor development appeared slightly delayed, while intellectual development was considered to be normal.

CaseNotHPOs: Corneal clouding (HP:0007957)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.006 μmol phenol/18 h/mg protein. Normal range of IDUA activity (n = 52, healthy volunteers): 0.143–0.351 μmol phenol/18 h/mg protein.

CaseUrineGAGs: Urinary GAG excretion - 101 mg GAG/mmol creatinine. The patient demonstrated increased excretion of GAGs, which were identified as HS and DS. Normal age adjusted range of urinary GAG excretion: 14–34 mg GAG/mmol creatinine.

CaseERT: The patient was initiated on enzyme replacement therapy (ERT) with weekly infusions of recombinant α-l-iduronidase 100 IE/kg

CaseBMT: The patient successfully received hematopoietic stem cell transplantation (HSCT) 4 months after ERT.

Variant1: c.1727+3G>C

Variant1ClinVarID: 4817926

Variant1CAID: CA91171181

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: Mother: c.208C>T (p.Q70X); 0.071 μmol phenol/18 h/mg protein (IDUA activity). Father: c.1727+3G>C; 0.079 μmol phenol/18 h/mg protein (IDUA activity).

PreviouslyPublished N/A

Case#: Patient 3

DiseaseAssertion: MPS1

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: CA204563

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

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A