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#: 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

Case#: Patient 1, 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.1487C>G (p.P496R)

Variant1ClinVarID: 496861

Variant1CAID: CA2802275

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

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

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 30, 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.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 79, Turkey

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.1727+6T>A

Variant1ClinVarID: 2203499

Variant1CAID: CA2580070698

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 21394825

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 13, 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.265C>T (p.R89W)

Variant1ClinVarID: 580286

Variant1CAID: CA2801156

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

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 19, 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.1727+1G>A

Variant1ClinVarID: 638077

Variant1CAID: CA355965296

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

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 33, 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.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

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#: Proband is female. Proband was 1 at the time her sample was collected.

DiseaseAssertion: MPS I, Hurler, Scheie, Hurler-Scheie syndrome

FamilyInfo: No family information provided

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: No iduronidase enzyme assay results mentioned for this proband. Testing was done from a fibroblast line.

CaseUrineGAGs: Urine GAG levels for proband not mentioned.

CaseERT: Don't know

CaseBMT: Don't know

Variant1: p.Trp402X

Variant1ClinVarID:

Variant1CAID: PA3051368272

Variant2: p.Trp402X

Variant2ClinVarID:

Variant2CAID: PA3051368272

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental testing results available

PreviouslyPublished No mention of previous publication

Case#: Patient 6, male, 11.5 months (age at HSCT), 8.1 months (age at ERT).

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Veno-occlusive disease (VOD), CMV reactivation

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.05 (at diagnosis), 33.8 (after HSCT) Units not provided.

CaseUrineGAGs: N/A

CaseERT: Yes - 112 days duration

CaseBMT: Yes - Through a sibling with stem cells sourcing from the BM (bone marrow).

Variant1: c.1882C>T (p.R628X)

Variant1ClinVarID: 550421

Variant1CAID: CA2802462

Variant2: c.1882C>T (p.R628X)

Variant2ClinVarID: 550421

Variant2CAID: CA2802462

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 8, male, 5 months (age at HSCT), 0.9 months (age at ERT)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Veno-occlusive disease (VOD), adenovirus infection

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.06 (at diagnosis), 20.1 (after HSCT) Units not provided.

CaseUrineGAGs: N/A

CaseERT: Yes - 124 days duration

CaseBMT: Yes - Through a sibling with stem cells sourcing from the BM (bone marrow).

Variant1: c.1882C>T (p.R628X)

Variant1ClinVarID: 550421

Variant1CAID: CA2802462

Variant2: c.1882C>T (p.R628X)

Variant2ClinVarID: 550421

Variant2CAID: CA2802462

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#: Hein Proband, Australian

DiseaseAssertion: MPS I, Hurler

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: no detectable α-l-iduronidase activity in skin fibroblast extracts without treatment, "These MPS I patients all had symptoms typical of classical Hurler syndrome."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: DNA sequence analysis, ABI PRISM® dGTP BigDye™ Terminator v3.0 Ready Reaction Cycle Sequencing Kit

PreviouslyPublished: n/a

Variant: Q400X/IVS9-1g→t

ClinVar: 1683229

CAID: CA355963534

SupplementalData: 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: 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#: 206 3.1yrs male, age at initial diagnosis 1.8 yrs DiseaseAssertion: MPS IH FamilyInfo:Nil CasePresentingHPOs: CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: IDUA activity: low leukocyte IDUA enzyme activity CaseUrineGAGs: CaseERT: 1 yr on ERT, then study drug, valanafusp alpha, also called AGT-181 for 12 months

CaseBMT: Yes, failed bone marrow transplant PreviouslyPublished Don't know Variant1:p.W402X Variant1ClinVarID: 11908 Variant1CAID: CA220498 Variant2:p.W402X Variant2ClinVarID: 11908 Variant2CAID: CA220498

Case#: Patient A, male, 11 months (age of diagnosis), at 12 years of age (age at report) he has cognitive status of 8 years.

DiseaseAssertion: MPS1-Hurler

FamilyInfo: Mother and father were tested - see maternal genotype below.

CasePresentingHPOs: N/A

CaseHPOFreeText: Splenectomy procedure conducted

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: α-L-iduronidase showed a profound deficiency (0.2 nmoles/17 h/mg, with a normal range of 25–90)

CaseUrineGAGs: N/A

CaseERT: Yes starting at 13 months

CaseBMT: Yes received an allogenic stem cell transplant at 1 year and 4 months.

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: Mother was heterozygous for c.208C>T while father was negative.

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#: Functional assay variant with a clinical significance of having conflicting interpretations.

DiseaseAssertion: MPS-I

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.1345C>A (p.H449N)

Variant1ClinVarID: 350230

Variant1CAID: CA2802233

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of having conflicting interpretations.

DiseaseAssertion: MPS-I

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.1577T>C (p.L526P)

Variant1ClinVarID: 567566

Variant1CAID: CA2802300

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of being a VUS.

DiseaseAssertion: MPS-I

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.904C>A (p.P302T)

Variant1ClinVarID: 1067236

Variant1CAID: CA355962529

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of being a VUS.

DiseaseAssertion: MPS-I

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.787A>T (p.R263W)

Variant1ClinVarID: 550605

Variant1CAID: CA2802085

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of being a VUS.

DiseaseAssertion: MPS-I

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.1757C>T (p.S586P)

Variant1ClinVarID: 571910

Variant1CAID: CA2802396

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of pathogenic.

DiseaseAssertion: MPS-I

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.1469T>C (p.L490P)

Variant1ClinVarID: 11919

Variant1CAID: CA220503

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

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#: TW1-3 ID number, Table S1.1 of Supplementary Material. Female, 1-2 years old (age at first symptoms), 1 year and 6 months old (age at diagnosis). Stored Frozen (-20ºC)

DiseaseAssertion: Severe MPS-I

FamilyInfo: Twin of patient TW1-2.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 589 fmol/punch

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11927

Variant1CAID: CA256128

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

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 1.1% residual activity at 37 °C

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.0 ± 0.4 nmol/mg/h IDUA activity at 37 °C

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.826G>A (p.E276K)

Variant1ClinVarID: 3233261

Variant1CAID: CA355962355

Variant2: c.826G>A (p.E276K)

ClinVarID: 3233261

Variant2CAID: CA355962355

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 0.2% residual activity at 37 °C

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.5 ± 0.1 nmol/mg/h IDUA activity at 37 °C

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

ClinVarID: 558189

Variant2CAID: CA2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: P2 8yrs male, age at initial diagnosis 5 yrs, age at definitive diagnosis 8 yrs DiseaseAssertion: mucopolysacchari- dosis type I (MPS I FamilyInfo:Nil CasePresentingHPOs: HP:0012185 (Constrictive median neuropathy) HP:0001376 (Limitation of joint mobility ) HP:0001387 (Joint stiffness) CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: IDUA activity: undetectable CaseUrineGAGs: Chondroitin sulfate (urine): 5.4 mg/mmol creat. Dermatan sulfate (urine): 5.5 mg/mmol creat. Heparan sulfate (urine): 37 mg/mmol creat. Keratan sulfate (urine): 7.4 mg/mmol creat. Normal values : chondroitin sulfate: 6.1 ± 3.4 mg/mmol creat.; dermatan sulfate: 2.4 ± 0.7 mg/mmol creat.; heparan sulfate: 9.4 ± 5.3 mg/mmol creat.; keratan sulfate: 12.9 ± 7.6 mg/mmol creat.; CaseERT: Don't know

CaseBMT: Don't know Variant1: IDUA:c.1524+2T>A, NM_000203.5; Transcriptomic analysis confirmed an insertion of four nucleotides between exons 10 and 11 in IDUA due to the disruption of the cryptic donor splicing site of exon 10. Variant1ClinVarID: Variant1CAID: CA355964832 Variant2: IDUA:c.-87T>C, NM_000203.5; Gene Expression Analysis by Luciferase Reporter Assay - 87% reduction was recorded in the context of the mutant IDUA promoter compared to the wild-type promoter. Variant2ClinVarID: Variant2CAID: CA2586973509 AdditionalVariants: ParentalGenotype: c.1524+2T>A (paternal) c.-87T>C (maternal) PreviouslyPublished No

Case#: Patient 1 was biochemically diagnosed with MPS I because they showed an increase in urinary GAGs and a reduction in IDUA activity in leukocytes. Patient 1 was diagnosed at 2 years and 3 months.

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facies, corneal clouding, intellectual disability, skeletal abnormalities, cardiac abnormalities, and hepatosplenomegaly (HP:0000256, HP:0007957, HP:0001249, HP:0002360, HP:0001627, HP:0001433)

CaseHPOFreeText: N/A

CaseNotHPOs: Growth delay, hernias (HP:0001510, HP:0100790)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity of 1.92 nmol/mg/protein/hr. No reference range provided.

CaseUrineGAGs: 1115.4 CPC unit/g creatinine. No reference range provided.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.613_617dup (p.E207Afs*29)

Variant1ClinVarID: 11921

Variant1CAID: CA256123

Variant2: c.683delC (p.P228Hfs*6)

Variant2ClinVarID: N/A

Variant2CAID: CA2580610937

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 7 was biochemically diagnosed with MPS I because they showed an increase in urinary GAGs and a reduction in IDUA activity in leukocytes. Patient 7 was diagnosed at 2 years and 11 months.

DiseaseAssertion: MPSI-S

FamilyInfo: N/A

CasePresentingHPOs: Coarse facies, corneal clouding, skeletal abnormalities, cardiac abnormalities, and hepatosplenomegaly (HP:0000256, HP:0007957, HP:0002360, HP:0001627, HP:0001433)

CaseHPOFreeText: N/A

CaseNotHPOs: Growth delay, hernias, intellectual disability (HP:0001510, HP:0100790, HP:0001249)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity of 2.35 nmol/mg/protein/hr. No reference range provided.

CaseUrineGAGs: 1011.7 CPC unit/g creatinine. No reference range provided.

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.1037T>G (p.L346R)

Variant2ClinVarID: 11927

Variant2CAID: CA256128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2 was biochemically diagnosed with MPS I because they showed an increase in urinary GAGs and a reduction in IDUA activity in leukocytes. Patient 2 was diagnosed at 1 year.

DiseaseAssertion: MPSI-H/S

FamilyInfo: N/A

CasePresentingHPOs: Coarse facies, corneal clouding, skeletal abnormalities, cardiac abnormalities, and hepatosplenomegaly (HP:0000256, HP:0007957, HP:0002360, HP:0001627, HP:0001433)

CaseHPOFreeText: N/A

CaseNotHPOs: Intellectual disability, growth delay, hernias (HP:0001249, HP:0001510, HP:0100790)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity of 2.8 nmol/mg/protein/hr. No reference range provided.

CaseUrineGAGs: 733.8 CPC unit/g creatinine. No reference range provided.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1163C>A (p.T388K)

Variant1ClinVarID: 198696

Variant1CAID: CA247499

Variant2: c.1163C>A (p.T388K)

Variant2ClinVarID: 198696

Variant2CAID: CA247499

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 1, male, 11 months (age of onset), 2 years (age at report)

DiseaseAssertion: MPS1

FamilyInfo: Born from a second-degree consanguineous marriage, has a healthy older brother.

CasePresentingHPOs: Claw hand deformity, extended Mongolian blue spot, hernia, macrocephaly, neurodevelopmental delay, dysostosis multiplex (HP:0034337, HP:0011369, HP:0100790, HP:0000256, HP:0012758, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: Intellectual disability (HP:0001249)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Low level of IDUA enzyme activity

CaseUrineGAGs: Negative GAG-excretion

CaseERT: N/A

CaseBMT: N/A

Variant1: c.523T>C (p.W175R)

Variant1ClinVarID: 226412

Variant1CAID: CA10576337

Variant2: c.523T>C (p.W175R)

Variant2ClinVarID: 226412

Variant2CAID: CA10576337

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2, female, 2 years (age of onset), 5 years (age at report)

DiseaseAssertion: MPS1

FamilyInfo: Born from a consanguineous marriage (second cousin parents), she had a twin sister that died a few weeks after birth. Her mother experienced intrauterine fetal death (IUFD) during her first pregnancy and after the second pregnancy infant died of congenital heart defects (CHD).

CasePresentingHPOs: Claw hand deformity, deafness, coarse facial features, dolichocephaly, neurodevelopmental delay, developmental regression (HP:0034337, HP:0000365, HP:0000256, HP:0000268, HP:0012758, HP:0002376)

CaseHPOFreeText: Began pronouncing words at 9 months, sitting at 10 months, and started walking at the age of 2. Her developmental conditions lapsed after the age of 2.

CaseNotHPOs: Intellectual disability (HP:0001249)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: GAG electrophoresis revealed increased amounts of DS and CS

CaseERT: She currently is taking Aldorazyme medication

CaseBMT: N/A

Variant1: c.612_615dupCTGC

Variant1ClinVarID: 226413

Variant1CAID: CA10576338

Variant2: c.612_615dupCTGC

Variant2ClinVarID: 226413

Variant2CAID: CA1057633

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 3 (19 y, male - cousin of Cases 1 and 2, symptom onset/pain+movement limittion 12y, diagnosis 19y))

DiseaseAssertion: Scheie syndrome

FamilyInfo: Male patient born to consanguineous parents

CasePresentingHPOs:

CaseHPOFreeText: electroneurology showed bilateral signs of mild median nerve suffering.

CaseNotHPOs: 0034337;HP:0001510; HP:0000943

CaseNotHPOFreeText: no coarse face, growth failure, other joint involvement, evidence of dysostosis multiplex of other bones. Normal intelligence, ophthalmologic, hearing and echocardiography, brain MRI

CaseEnzymeAssay: 0.57 (umol/g/h)

CaseUrineGAGs:

CaseERT: Yes, after diagnosis at 19y

CaseBMT:

Variant1:c.1189+4A>T

Variant1ClinVarID:

Variant1CAID: CA2586965965

Variant2: 1189+4A>T

Variant2ClinVarID:

Variant2CAID: CA2586965965

AdditionalVariants:

ParentalGenotype:

PreviouslyPublished

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 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#: 51 year old patient, Italy, male

DiseaseAssertion: MPS1-H/S

FamilyInfo: This patient also had an affected MPS1-H/S sibling. Their mother was not only an MPS1 carrier but also had Fabry disease.

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.1189+5G>A

Variant1ClinVarID: 551848

Variant1CAID: CA658823290

Variant2: c.46_57del (p.Ser16_Ala19del)

Variant2ClinVarID: 92643

Variant2CAID: CA220509

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished Yes - PMID: 21394825

Case#: Infant #2, male.

DiseaseAssertion: MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 1.50 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)

CaseUrineGAGs: DMB/Cre. Ratio - 34.02, DS - 0.11, HS - 0.17, KS - 0.53 GAG quantifications (DMB/Cre ratio) and the normal reference values based on the age groups: <6 mos: <70.68 mg /mmol cre.; 6 mos–2 yrs: <46.80 mg /mmol cre.; 2–17 yrs: <20.98 mg /mmol cre.; and >18 yrs: <12.62 mg /mmol cre. Quantitative analyses of GAG-derived disaccharides (DS, S, or KS) by tandem mass spectrometry assay. The normal cut-off values: DS < 0.80 μg/mL; HS < 0.78 μg/mL; and KS < 7.90 μg/mL.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1395delC (p.G466AfsTer59)

Variant1ClinVarID: 929236

Variant1CAID: CA549264595

Variant2: c.1081G>A (p.A361T)

Variant2ClinVarID: 92624

Variant2CAID: CA145865

AdditionalVariants: c.1816G>T (p.V606L), ClinVarID: 2432754, CAID: CA2802416

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#:4. 1.5 year Male, diagnosed at 1.3 years DiseaseAssertion:MPS1H FamilyInfo:NA CasePresentingHPOs:NA CaseHPOFreeText:NA CaseNotHPOs:NA CaseNotHPOFreeText:NA CaseEnzymeAssay:Undetectable CaseUrineGAGs:NA CaseERT:NA CaseBMT:Yes, matched sibling donor, Post HSCT 13.24 nmol/h/mg of protein ( α-l-Iduronidase Levels) Variant1:IDUA : c.1598C>G Variant1ClinVarID:11910 Variant1CAID: CA256112 Variant2:IDUA: c.1205G>A Variant2ClinVarID: 11908 Variant2CAID:CA220498 AdditionalVariants: ParentalGenotype: PreviouslyPublished

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#: IV-2, Male, Yemeni, deceased at age 5 years

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Parents are consanguineous first cousins (Pedigree figure #1)

CasePresentingHPOs: HP:0001640, HP:0000280, HP:0002516 (Cardiomegaly, Coarse Facial Features, Intracranial hypertension)

CaseHPOFreeText: Dysplasia

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: N/A

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: Both parents are heterozygous for the c.657delA variant of the gene (see pedigree @ figure#1)

PreviouslyPublished N/A

PMID: 24314423 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive

PMID: 36541357

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: MPS 1 patient

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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.1877G>A (p.W626X)

Variant2ClinVarID: 928997

Variant2CAID: CA355965968

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: MPS 1 patient

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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.501C>G (p.Y167X)

Variant2ClinVarID: 92644

Variant2CAID: CA220511

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 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

Case#: P1-IDUA, F Europeanin Italy DiseaseAssertion: MPS 1: Psuedo/Hurler FamilyInfo: CasePresentingHPOs: CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: NBS 1.36 triplex/3.4 single CaseUrineGAGs: CaseERT: CaseBMT: Variant1: c.246C > G Variant1ClinVarID: 92637 Variant1CAID: CA220506 Variant2: c.1205G > A Variant2ClinVarID: 11908 Variant2CAID: CA220498 AdditionalVariants: ParentalGenotype: PreviouslyPublished

PMID: 30442156 Gene: IDUA Disease: MPS1 Inheritance: Autosomal recessive

Case#: Patient 27 (see Table 2), Gestational age unavailable

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 1.70 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.979G>C (p.A327P)

Variant1ClinVarID: 167190

Variant1CAID: CA:234128

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

Variant2ClinVarID: 558189

Variant2CAID: CA:2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 12 (see Table 2), 40 weeks (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: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.653T>C (p.L218P)

Variant1ClinVarID: 222995

Variant1CAID: CA:356986

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

Variant2ClinVarID: 222995

Variant2CAID: CA:356986

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#: 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#: 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#: PKMPS1P11, 8 years old (age at presentation), female, Pakastani. Poor performance in school due to difficulty in writing.

DiseaseAssertion: MPS-I

FamilyInfo: Born to parents in a consanguineous marriage

CasePresentingHPOs: Coarse facial features, joint stiffness, stunted and mild thoracic kyphosis (HP:0000256, HP:0001387, HP:0002808)

CaseHPOFreeText: Widening of the wrist

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1469T>C (p.L490P)

Variant1ClinVarID: 11919

Variant1CAID: CA220503

Variant2: c.1469T>C (p.L490P)

Variant2ClinVarID: 11919

Variant2CAID: CA220503

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#:Patient Sample unique ID 2

DiseaseAssertion:MPS type I-Hurler children

FamilyInfo:None

CasePresentingHPOs:None

CaseHPOFreeText:None

CaseNotHPOs:Obstructive sleep apnea, HP:0002870

CaseNotHPOFreeText:None

CaseEnzymeAssay:None

CaseUrineGAGs: Tested but amounts not reported

CaseERT:No

CaseBMT:Hematopoietic stem cell transplantation

Variant1: c.979G>C

Variant1ClinVarID:167190

Variant1CAID:CA234128

Variant2:None

Variant2ClinVarID:None

Variant2CAID:None

AdditionalVariants:None

ParentalGenotype:None provided

PreviouslyPublished:N/A

PMID:20553232

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

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