Case#: Patient 6 (see Table 2), male, 16.7 years old (age at report), 10.4 years (duration of treatment), 4 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0002360 (Sleep abnormality)

CaseHPOFreeText: Psychiatric problems

CaseNotHPOs: HP:0000238, HP:0002176 (Hydrocephalus, spinal cord compression)

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: (Int3-2a>g) Current HGVS nomenclature is c.386-2A>G.

Variant2ClinVarID: 222994

Variant2CAID: CA356991

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2 (see Table 2), male, 18.3 years old (age at report), 9.1 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.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 4 (see Table 2), female, 19.8 years old (age at report), 9.7 years (duration of treatment), 8 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0000238, HP:0002360 (Hydrocephalus, sleep abnormality)

CaseHPOFreeText: Shunt placement, psychiatric problems

CaseNotHPOs: HP:0002176 (Spinal cord compression)

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.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 1 (see Table 2), female, 18.6 years old (age at report), 5.9 years (years of treatment), 6 surgeries.

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0002176, HP:0002360 (Spinal cord compression, sleep abnormality)

CaseHPOFreeText: Psychiatric problems

CaseNotHPOs: HP:0000238 (Hydrocephalus)

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.63delC (p.P22Rfs*86) Known HGVS nomenclature is c.65del as there is a run of 5 C's.

Variant2ClinVarID: 929238

Variant2CAID: CA437911597

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: L238Q

Variant1ClinVarID: 265418

Variant1CAID: CA2802065

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

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