Case#: 0.1% residual activity at 37 °C

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.2 ± 0.1 nmol/mg/h IDUA activity at 37 °C

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)

ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 70, Spain

DiseaseAssertion: N/A

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.1189+4A>G

Variant2ClinVarID: N/A

Variant2CAID: CA2586965964

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 38, Poland

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.979G>C (p.A327P)

Variant1ClinVarID: 167190

Variant1CAID: CA234128

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 51, Poland

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: Nomenclature in the paper - c.1398delC; current nomenclature - c.1400del p.Pro467ArgfsTer?)

Variant2ClinVarID: 3910474

Variant2CAID: CA2586965982

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 11, Italy

DiseaseAssertion: MPS1-H/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.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.532G>A (p.E178K)

Variant2ClinVarID: 2203495

Variant2CAID: CA355961709

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 69, Spain

DiseaseAssertion: N/A

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.1187T>C (p.L396P)

Variant2ClinVarID: 4689688

Variant2CAID: CA355963499

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 32, Italy

DiseaseAssertion: MPS1-H/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.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1225G>A (p.G265R)

Variant2ClinVarID: 1084956

Variant2CAID: CA91169920

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 10, Italy

DiseaseAssertion: MPS1-H/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.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1603C>T (p.L535F)

Variant2ClinVarID: 638076

Variant2CAID: CA355865038

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient C

DiseaseAssertion: N/A

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.266G>A (p.R89Q)

Variant2ClinVarID: 11922

Variant2CAID: CA256124

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#:Patient Sample unique ID 63, 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:Carrier

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 0.175 (2.1) umol/L/h (%DMA) during new born screening through dried blood spot (plasma) and 7.7 pmol/punch/h Confirmatory IDUA enzyme measured at follow-up appointment

CaseUrineGAGs: DS 7.4 g/mol creatinine and HS 5.8 g/mol creatinine (Normal)

CaseERT:No

CaseBMT:No

Variant1:heterozygous pathogenic: c.1205G>A; p.W402** (Normal examination)

Variant1ClinVarID:11908

Variant1CAID:CA220498

Variant2:heterozygous VUS: c.1417A>T; p.T473S (Carrier)

Variant2ClinVarID:2450304

Variant2CAID:CA346704036

AdditionalVariants:heterozygous PD: c.246C>G; p.H82Q (ClinVarID: 92637, CAID:CA220506)

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: Not provided

CaseUrineGAGs: Abnormal

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#: No additional case information provided

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Abnormal

CaseUrineGAGs: Abnormal

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1402+1G>T

Variant2ClinVarID: 1323099

Variant2CAID: CA355964387

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 27 (Table 3)

DiseaseAssertion: Severe naïve MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X) Listed in Table 3 as c.12095G>A

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1205G>A (p.W402X) Listed in Table 3 as c.12095G>A

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 39 (Table 3)

DiseaseAssertion: Severe MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 41 nmol/h/mg per DBS (dried blood spots) determined during NBS. 60.2 DBS protein concentration determined by Immuno-SRM (pmol/L).

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 280976

Variant2CAID: CA2802455

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 37 (Table 3)

DiseaseAssertion: Severe MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 13 nmol/h/mg per DBS (dried blood spots) determined during NBS. 21.1 DBS protein concentration determined by Immuno-SRM (pmol/L).

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Yes

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#: Patient 29 (Table 3)

DiseaseAssertion: Severe naïve MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: <1 nmol/h/mg per DBS (dried blood spots) determined during NBS

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1524+1G>T

Variant2ClinVarID: 555169

Variant2CAID: CA355964830

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 28 (Table 3)

DiseaseAssertion: Severe naïve MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X) Listed in Table 3 as c.12095G>A

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1205G>A (p.W402X) Listed in Table 3 as c.12095G>A

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 26, born in 2010 (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: Cataract, retinopathy (HP:0000518, HP:0000488)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 71 ng/mol (43 weight matched enzyme reference assay)

CaseUrineGAGs: 0.42 DS/CS

CaseERT: Yes

CaseBMT: Yes, Cord

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 12, born in 2006 (paper published in 2017), 13 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: 41.12 ng/mol (17.84 weight matched enzyme reference assay)

CaseUrineGAGs: 0.37 DS/CS

CaseERT: Yes

CaseBMT: Yes, Cord

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 23, born in 1992 (paper published in 2017), 15 months (age at first treatment), 18 months (age at last 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: 36.55 ng/mol (67.98 weight matched enzyme reference assay)

CaseUrineGAGs: 0.60 DS/CS

CaseERT: No

CaseBMT: Yes, MUD

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 21, born in 2000 (paper published in 2017), 22 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: 48 ng/mol (36 weight matched enzyme reference assay)

CaseUrineGAGs: 0.63 DS/CS

CaseERT: No

CaseBMT: Yes, MUD

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.64_65delC (p.Pro22GlyfsTer?)

Variant2ClinVarID: N/A

Variant2CAID: CA3246685724

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 17, born in 2009 (paper published in 2017), 1 year (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: 48 ng/mol (38 weight matched enzyme reference assay)

CaseUrineGAGs: 0.42 DS/CS

CaseERT: Yes

CaseBMT: Yes, MUD

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 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 13, born in 2010 (paper published in 2017), 16 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: 55 ng/mol (36 weight matched enzyme reference assay)

CaseUrineGAGs: 0.28 DS/CS

CaseERT: N/A

CaseBMT: Yes, MUD (GOS)

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 14, born in 1998 (paper published in 2017), 19 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding, cataract (HP:0007957, HP:0000518)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy (HP:0000488)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 31.4 ng/mol (60.7 weight matched enzyme reference assay)

CaseUrineGAGs: 0.60 DS/CS

CaseERT: No

CaseBMT: Yes, MUD

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 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 7, born in 2005 (paper published in 2017), 16 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: 62.57 ng/mol (34.3 weight matched enzyme reference assay)

CaseUrineGAGs: 0.59 DS/CS

CaseERT: No

CaseBMT: Yes, Cord

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.386-2A>G

Variant2ClinVarID: 222994

Variant2CAID: CA356991

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2, born in 2000 (paper published in 2017), 18 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: 28 ng/mol (38 weight matched enzyme reference assay)

CaseUrineGAGs: 0.36 DS/CS

CaseERT: No

CaseBMT: Yes, MUD

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 7, female, 8.2 months (age at diagnosis), 11.4 months (age at HSCT), 9.7 - 14.0 months (age at ERT), 4 MRI + neuropsychological observations over the course of 9 years.

DiseaseAssertion: MPS-1H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 68.0 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.1205G>A (p.W402)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: CA-118 ID number, Table S1.1 of Supplementary Material. Male, at birth (age at first symptoms), 1 year and 3 months old (age at diagnosis). Failed newborn hearing test, behind on milestones such as walking, sitting, and crawling. Goes to PT weekly. Stored frozen (-20ºC) 2.8 yr

DiseaseAssertion: Severe MPS-I

FamilyInfo: N/A

CasePresentingHPOs: Delayed speech, kyphosis, enlarged tonsils, corneal clouding, constipation, hearing impairment, central sleep apnea, obstructive sleep apnea, (HP:0000750, HP:0002808, HP:0030812, HP:0007957, HP:0002019, HP:0000365, HP:0010536, HP:0002870)

CaseHPOFreeText: Leaky mitral valve, physical delays.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 933 fmol/punch

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

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

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: NC-700 ID number, Table S1.1 of Supplementary Material. Female, 8 months old (age at first symptoms), 1 year and 2 months old (age at diagnosis). Stored ambient 1.7 yr.

DiseaseAssertion: Severe MPS-I

FamilyInfo: N/A

CasePresentingHPOs: Recurrent ear infections, kyphosis, gross motor delay, hearing loss, corneal clouding (HP:0410018, HP:0002808, HP:0002194, HP:0000365, HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 1142 fmol/punch

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1032C>G (p.Y344X) is included in the table but according to the CilnGen allele registry, this genotype does not exist.

Variant1ClinVarID: N/A

Variant1CAID: N/A

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: CA-119 ID number, Table S1.1 of Supplementary Material. Male, at birth (age at first symptoms), 15 years and 6 months old (age at diagnosis). Stored frozen (-20ºC) 32 yr. May be the sibling of CA-120 due to closeness in ID numbers as well as having the same variants.

DiseaseAssertion: Attenuated MPS-I

FamilyInfo: N/A

CasePresentingHPOs: Premature birth, hernia (3), ear infections, joint contractures (HP:0001622, HP:0100790, HP:0410018, HP:0002828)

CaseHPOFreeText: Lung issues, hernia, spine heart (No additional information about these symptoms provided)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 393 fmol/punch

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1651-7C>T

Variant1ClinVarID: 1147380

Variant1CAID: CA438057995

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Subject 3, female, in her 20s (age at enrollment)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: HP:0002176 (Spinal cord compression)

CaseHPOFreeText: Disappearance of Hoffmann's reflex

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Enzyme replacement therapy with laronidase, did not enroll in extension study

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1577T>C (p.L526P)

Variant2ClinVarID: 567566

Variant2CAID: CA2802300

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Subject 2, female, in her 10s (age at enrollment)

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0000012, HP:0000020, HP:0007340, HP:0002176 (Urinary urgency, urinary incontinence, lower limb muscle weakness, spinal cord compression)

CaseHPOFreeText: Anti-iduronidase antibodies, leukocytes

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Off-study, off-label with intrathecal laronidase beginning ~16 months prior to enrollment in the extension study, received prophylaxis with oral prednisone prior to intrathecal laronidase.

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.713T>A (p.L238Q)

Variant2ClinVarID: 265418

Variant2CAID: CA2802065

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Subject 4, male in his 10s (age at enrollment), died in his sleep within the first 48 hours of the initial dose during pilot study.

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0002176, HP:0001638 (Spinal cord compression, cardiomyopathy)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Enzyme replacement therapy with laronidase

CaseBMT: N/A

Variant1: c.1208G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.713T>A (p.L238Q)

Variant2ClinVarID: 265418

Variant2CAID: CA2802065

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 4 (see Table 2), 39 weeks, 6 days (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Upper respiratory tract involvement

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.25 nmol x mg-1 × hr-1

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 5 (see Table 2), 37 weeks, 5 days (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.26 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.46_57del (p.Ser16_Ala19del) (c.134del12)

Variant2ClinVarID: 92643

Variant2CAID: CA220509

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished c.134del12 is based on old numbering. The variant is referred to as "134del12" in older papers. The correct name is: NM_000203.5(IDUA):c.46_57del (p.Ser16_Ala19del)

Case#: Patient 1 (see Table 2), 37 weeks (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Inguinal hernia (HP:0000023)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: 0.31 nmol x mg-1 × hr-1

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 19 (see Table 2), 38 weeks (Gestational age)

DiseaseAssertion: MPS1-H/S

FamilyInfo: Sibling of Patient 20 (see Table 2)

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: 0.92 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1044C>A (p.N348K)

Variant2ClinVarID: N/A

Variant2CAID: CA:355963142

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 3 (see Table 2), 40 weeks (Gestational age)

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.208C>T (p.Q70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 24 (see Table 2), 40 weeks (Gestational age)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: 1.05 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1148G>A (p.R383H)

Variant2ClinVarID: 558189

Variant2CAID: CA:2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 10 (see Table 2), Gestational age not available

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Upper respiratory tract involvement

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.653T>C (p.L218P)

Variant2ClinVarID: 222995

Variant2CAID: CA:356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 1, male, 15 months (age at diagnosis), 20.5 months (age at HSCT), weight of 12.7 kg (at HSCT), 5.8 years (age at report). Upon HSCT the patient made neurodevelopmental progress and attended kindergarten, he still had severe mental disabilities and aggressive behavior problems.

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Neurodevelopmental delay, speech delay, mild lumbar hyperlordosis (HP:0012758, HP:0000750, HP:0002938)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Activity of alpha-L-iduronidase in leukocytes was normal from 2 months after cessation of ERT.

CaseUrineGAGs: Patient had normal excretion of total urine GAGs.

CaseERT: Yes - 21 weeks of ERT before HSCT. Continued until day 107 of HSCT.

CaseBMT: Yes - interval diagnosis for HSCT (22 weeks). The donor was female and unrelated.

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: One patient from The Netherlands

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.979G>C (p.A327P)

Variant1ClinVarID: 167190

Variant1CAID: CA234128

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

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: 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.964delC in paper but correct nomenclature is c.876delC (p.Asp292GlufsTer25)

Variant1ClinVarID: 456720

Variant1CAID: CA658657370

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: c.1360G>A (p.V454I) and c.1467C>T (p.R489=)

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: One patient from The Netherlands

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.1466G>C (p.R489P)

Variant1ClinVarID: 1518214

Variant1CAID: CA355964650

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient is 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.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: G387+6C>T on same allele

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.223G>C (p.A75T)

Variant1ClinVarID: 222993

Variant1CAID: CA356994

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 9, 9-years old at the start of ERT

DiseaseAssertion: MPS1-H/S - confirmed diagnosis of MPS 1 by enzymatic and mutation analysis

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: Urine GAGs are displayed in a figure and show the level at the start of ERT to 18-months later. At the start, urine GAGs appear to be close to 25 mg/mmol creatinine. After 18-months they decreased to be between 10-15 mg/mmol creatinine. Normal values for 2-10-year olds are 5-15 mg/mmol creatinine.

CaseERT: Yes - started at 9-years old and was given once every week

CaseBMT: No

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1513C>G (p.R505G)

Variant2ClinVarID: 1482722

Variant2CAID: CA355964784

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient is 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.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: G387+6C>T on same allele

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient is 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.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: G387+6C>T on same allele

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient III, origin of proband is Holland

DiseaseAssertion: Scheie syndrome (S)

FamilyInfo: No family information provided

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: 0.60 nmol/mghour IDUA enzyme activity in proband. Reference range of IDUA enzyme activity is 14.0 - 40.0 nmol/mghour

CaseUrineGAGs: Information not stated in this paper

CaseERT: Don't know

CaseBMT: Don't know

Variant1: c.1205G>A, p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: Not identified in this study

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental information provided

PreviouslyPublished: I do not believe this proband was previously published. The paper states that variant "c.1205G>A 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#:UNIGEi001-A, 2-year-old, Male, Caucasian, MPS1-H diagnosed by Division of Metabolism and Children's Research Center of University Children's Hospital of Zürich (Switzerland) 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: Don't know CaseBMT: Don't know Variant1: NM_000203.5(IDUA):c.1073_1093del (p.His358_Thr364del) Variant1ClinVarID: 557260 Variant1CAID: CA658823289 Variant2: NM_000203.4(IDUA):c.1205 G>A (p.Trp402Ter) Variant2ClinVarID: 11908 Variant2CAID: CA220498 AdditionalVariants: N/A ParentalGenotype: N/A PreviouslyPublished N/A

Case#: 6, Male, 1 month (onset), 18 months (diagnosed), 18 months (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0001387, HP:0002240, HP:0000501, HP:0000280, HP:0000943, HP:0007957 (Joint Stiffness, Hepatomegaly (moderate), Glaucoma, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (delayed since 1y), LV hypertrophy (at 3y), Inguinal bilat. and umbilical hernia)

CaseNotHPOs: HP:0001744 (Splenomegaly)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.W402X (not identified)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: p.A8, p.A20, p.N297

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#: 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#: 1, Male, 4 months (onset), 2 years (diagnosed), 2 years (report), deceased

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0004322, HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0001639, HP:0001537, HP:0011947, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Macrocephaly, Joint Stiffness, Hepatomegaly (severe), Splenomegaly (severe), Hypertrophic Cardiomyopathy, Umbilical Hernia, Respiratory Infections, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Developmental Quotient 54-62 at 2y), Systolic Murmur (3/6),

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.W402X

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 2, Male, 1 year (onset), 13 months (diagnosed), 5 years (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0001387, HP:0002240, HP:0001744, HP:0001537, HP:0000023, HP:0000365, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Joint Stiffness, Hepatomegaly (moderate before HSCT, mild after HSCT), Splenomegaly (mild), Umbilical Hernia, Inguinal Hernia, Deafness, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Normal development till 1y, developmental quotient 79 at 2y), Systolic Murmur (1/6; Ejection fraction of 68% at 4 years old)

CaseNotHPOs: HP:0004322, HP:0000256 (Short Stature, Macrocephaly)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation in 2 years (chimerism)

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#: Family 7, 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.1650+5G>A; IVS12+5G>A in the paper

Variant2ClinVarID: 92634

Variant2CAID: CA220504

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 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#: Family 24, Ireland

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: c.1487C>T (p.P496L)

Variant2ClinVarID: 551675

Variant2CAID: CA91170412

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 8, 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 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#: 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

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

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.158+1G>A

Variant1ClinVarID: 526835

Variant1CAID: CA355945713

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

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

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.36_44delGCTCCTGGC (p.Leu13_Ala15del)

Variant1ClinVarID: 3720558

Variant1CAID: CA645372295

Variant2: c.1205G>A (W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.794G>A (p.G265D)

Variant1ClinVarID: 2203496

Variant1CAID: CA91168317

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

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#: Male, first evaluated at 3.5 years, diagnostic studies described in paper at age 4.5 years, at time of report 11 years

DiseaseAssertion: Mucopolysaccharidosis Type I and Type II

FamilyInfo:Clinically normal sister, mother and father; parents denied consanguinity; extensive histocompatibility typing of all family members confirmed relationships and did not suggest consanguinity; Maternal uncle died at 11 years having "coarse facial features" but not diagnostic testing. Pedigree, Figure 7, page 82.

CasePresentingHPOs: HP:0000943 (dysostosis multiplex); HP:0000280 (course facial features)

CaseHPOFreeText: at 3.5 years "...gross motor delay, mild expressive language delay, and progressive changes in facial features and joints...noted to be a noisy breather and have a history of frequent ear infections...prominent metopic suture and facial features were said to be coarsened" Height 50th%, weight 95th%, head circumference >98th%. At 11 years of age reported to show progressive intellectual deterioration.

CaseNotHPOs:

CaseEnzymeAssay: Table 2 (page 79): leukocyte IDUA (alpha-L) activity absent (<1.0 nmol/mg/h), plasma IDUA alpha-L <0.20 MU/ml/h); plasma IDS activity was undetectable (0.0 U/mg/h)

CaseUrineAssay:Not reported

CaseERT:Don't know

CaseBMT:Don't know

Variant1:IDUA W402X

Variant1ClinVarID:11908

Variant1CAID:

Variant2: IDUA A300T

Variant2ClinVarID: 11923

Variant2CAID:

AdditionalVariants: IDS R468W (missense 1402C-->T), ClinVarID: 10497

ParentalGenoype:Mother, IDUA A300T and IDS R468W; Father, IDUA W402X

PreviouslyPublished:

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#: 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: CA356990

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 3 (see Table 2), male, 16.5 years old (age at report), 7.6 years (duration of treatment), 6 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0000238, HP:0002176, HP:0002360 (Hydrocephalus, spinal cord compression, sleep abnormality)

CaseHPOFreeText: Psychiatric problems

CaseNotHPOs: N/A

CaseNotHPOFreeText: Shunt placement

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.712T>A (p.L238Q) CDNA and protein change do not match. Known variant p.L238Q has a CDNA change of c.713T>A.

Variant1ClinVarID: 265418

Variant1CAID: CA2802065

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 5 (see Table 2), female, 17.8 years old (age at report), 0.3 years (duration of treatment), 7 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0000238, HP:0002176, HP:0002360 (Hydrocephalus, spinal cord compression, sleep abnormality)

CaseHPOFreeText: Shunt placement, psychiatric problems

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.712T>A (p.L238Q) CDNA and protein change do not match. Known variant p.L238Q has a CDNA change of c.713T>A.

Variant1ClinVarID: 265418

Variant1CAID: CA2802065

Variant2: c.1208G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 11 (see Table 2), male, 19 years old (age at report), 9.4 years (duration of treatment), 8 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0000238, HP:0002176 (Hydrocephalus, Spinal cord compression)

CaseHPOFreeText:

CaseNotHPOs: HP:0002360 (sleep abnormality)

CaseNotHPOFreeText: Shunt placement, psychiatric problems

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.265C>T (p.R89W)

Variant1ClinVarID: 580286

Variant1CAID: CA2801156

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient M (male) is an Italian boy who was diagnosed with MPS I by enzyme assay at 3 days of age. His weight was 7.5 kg (75th percentile), length was 67.0 cm (90th percentile), and head circumference was 43.0 cm (75th percentile).

DiseaseAssertion: MPS1-H/S

FamilyInfo: The patient is a younger asymptomatic sibling who was diagnosed with the disease because of his older affected sister. Two months before patient M birth, his 4.5-year-old sister, patient F, had been diagnosed with the Hurler-Scheie form of MPS I on the basis of clinical findings, an elevated urinary glycosaminoglycan level, and low α-l-iduronidase activity in leukocytes.

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: He did not develop coarse facial features, joint disease, or organomegaly, and he has shown no evidence of cardiac disease or skeletal abnormalities. He has shown no signs of dysostosis multiplex on radiographs, and his heart valves functioned normally and were not thickened or dysplastic.

CaseEnzymeAssay: N/A

CaseUrineGAGs: 651.7 μg/mg creatinine (normal value for age: 30–200 μg/mg); predominance of heparan sulfate and dermatan sulfate. Urinary glycosaminoglycan excretion decreased to normal levels for age within 4 months of therapy, with complete disappearance of dermatan and heparan sulfate bands on electrophoresis.

CaseERT: Yes - started laronidase at the age of 5 months. Weekly intravenous infusions of laronidase, at the standard dose of 100 U/kg of body weight. Over the following 5 years, treatment was administered regularly (only 3 infusions were missed), and it was well tolerated without any significant adverse effects.

CaseBMT: N/A

Variant1: c.12205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1603C>T (p.L535F)

Variant2ClinVarID: 638076

Variant2CAID: CA355965038

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient F (female), diagnosed at 4 years and 6 months on the basis of clinical findings, an elevated urinary glycosaminoglycan level, and low α-l-iduronidase activity in leukocytes. Patient F was 104.0 cm tall (75th percentile).

DiseaseAssertion: MPS1-H/S

FamilyInfo: The patient is an older sibling who was diagnosed with the disease and has an affected younger brother.

CasePresentingHPOs: Coarse facial features, joint stiffness, thick skin, corneal clouding, hepatosplenomegaly, dysostosis multiplex (HP:0000280, HP:0001387, HP:0001072, HP:0007957, HP:0001433, HP:0000943)

CaseHPOFreeText: Moderate mitral insufficiency with thickened valve leaflets and anterior edge prolapse; mild left atrium thickening and increased pulmonary pressure were also present. Radiographic skeletal examination showed several signs of hip hypoplasia, ovoid shape of lumbar vertebral bodies, V-shaped distal ulnar and radial extremities, and short and broad metacarpal bones. Although she had normal intelligence, she developed obstructive hydrocephalus, which required shunting at 7 months of age.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Low α-l-iduronidase activity in leukocytes

CaseUrineGAGs: Elevated urinary glycosaminoglycan levels

CaseERT: Yes - Patient F started laronidase at 5 years of age, also at the standard dose. After 5 years of therapy, she was 138.0 cm tall (90th percentile), her liver and spleen volume had normalized, her skin had become less thickened, and her shoulder flexion and extension were moderately improved. Her dysostosis multiplex, cardiac function, and corneal clouding (visual acuity: 10/10) had stabilized but were not improved.

CaseBMT: N/A

Variant1: c.12205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1603C>T (p.L535F)

Variant2ClinVarID: 638076

Variant2CAID: CA355965038

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 7, 6 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.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 3, 4 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.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#: P2, male, 1.8 years (age at HCT - hematopoietic cell transplantation), 14 iPS colonies per 100,000 cells (KC), 4 iPS colonies per 100,000 cells (MSC).

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: Yes - Donor cells were received from KC, keratinocytes, and MSC, mesenchymal stromal cells.

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#: Hein Proband, Australian

DiseaseAssertion: MPS I, attenuated

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: IDUA activity=0.43±0.06 pmol/min per mg

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod:

PreviouslyPublished: n/a

Variant: R628X/W402X

ClinVar: 11908; 550421

CAID: CA220498; CA2802462

SupplementalData: n/s

Case#: Patient 7, 6 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.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#: Sibling 2, Patient F, female, 17 years old (age at report)

DiseaseAssertion: MPS1

FamilyInfo: Affected younger sibling (Sibling 1)

CasePresentingHPOs: HP:0000280, HP:0034337, HP:0001376, HP:0007957, HP:0000540, HP:0000483, HP:0000388, HP:0008513, HP:0000943, HP:0006536 (Coarse facial features, claw hand deformity, limitation of joint mobility, corneal clouding (unchanged since ERT), hyperopia (age 11), astigmatism (age 11), otitis media, mild bilateral conductive hearing (age 16), multiplex dysostosis, airway obstruction)

CaseHPOFreeText: Joint disease with limitation of range of motion of both proximal and distal joints, straight spine, cannot raise arms above head, median nerve compression, bilateral elongation of the Achilles tendon.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Respiratory or sleep disturbances, no significant progression of previously reported moderate mitral insufficiency with thickened valve leaflets, anterior edge prolapse and mild left atrium thickening, no improvement of her moderately severe dysostosis multiplex with evidence of slight worsening of thoracic vertebral changes but stable cervical and hand findings, no white matter alterations

CaseEnzymeAssay: N/A

CaseUrineGAGs: At the age of 5 years, before ERT, were 18.2 μg/ml (nv: 5.27 μg/ml ± 3.01) with a CS/DS ratio of 25/75 (nv: 100/0); after 6, 9 and 10 year of ERT, plasma GAGs have remained within the normal range for age.

CaseERT: Yes

CaseBMT: N/A

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

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1603C>T (p.L535F)

Variant2ClinVarID: 638076

Variant2CAID: CA355965038

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Case 1, male, ~40 years old (age at onset of symptoms), 56 years old (age at diagnosis), height of 177 cm, weight of 84 kg, BMI of 26.9 kg/m2.

DiseaseAssertion:MPS1

FamilyInfo: N/A

CasePresentingHPOs: Visual impairment, chest infections, pericentral retinitis pigmentosa, retinopathy (HP:0000505, HP:0002783, HP:0007947, HP:0000488)

CaseHPOFreeText: Electrocardiogram: Left ventricular hypertrophy on voltage criteria, right sensorineural deafness, changes in lumbar spine (present significantly), T wave abnormalities were observed.

CaseNotHPOs: Intellectual disability (HP:0010864)

CaseNotHPOFreeText: Ultrasound scan of liver/spleen/hernia and pulmonary function tests were normal.

CaseEnzymeAssay: 0.3 nmol/mg/hr (13.0–111.0 nmol/mg/hr reference range)

CaseUrineGAGs: 5.4 mg/mmol (0-8.0 mg/mmol reference range) per author Karolina Stepien

CaseERT: N/A

CaseBMT: N/A

Variant1: c.794G>A (p.G265D)

Variant1ClinVarID: 2203496

Variant1CAID: CA91168317

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

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: No mention about additional variants per author Karolina Stepien

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Male, 2-year old

DiseaseAssertion: MPS1-H

FamilyInfo: Not provided

CasePresentingHPOs: Not provided

CaseHPOFreeText: NA

CaseNotHPOs: Not provided

CaseNotHPOFreeText: NA

CaseEnzymeAssay: MPS1-H fibroblasts exhibited no activity of IDUAα (0.01 ± 0.02 nmol/mg/min); iPSC clones were devoid of IDUAα activity

CaseUrineGAGs: Not provided

CaseERT: Don't know

CaseBMT: Don't know

Variant1: NM_000203.5(IDUA):c.1073_1093del (p.His358_Thr364del)

Variant1ClinVarID:557260

Variant1CAID:

Variant2: NM_000203.4(IDUA):c.1205 G>A (p.Trp402Ter)

Variant2ClinVarID:11908

Variant2CAID:

ParentalGenotype: Not provided

PreviouslyPublished: Authors reference [30]: PMID: 31678774 DOI: 10.1016/j.scr.2019.101604