Case#: Patient 14 (group 2), Poland, male 5 years old (age at diagnosis), 15 years old (age at baseline), 19 years old (current age)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: Limitation of join mobility, joint stiffness (HP:0001376, HP:0001387)

CaseHPOFreeText: Patients in group 2 had normal mental development or only slightly delayed mental development and, therefore, could undergo active physical rehabilitation.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Diagnosis of MPS I was confirmed by the biochemical determination of α-L-iduronidase activity deficiency in leukocytes and by molecular analysis.

CaseUrineGAGs: N/A

CaseERT: Yes, weekly infusions for 52-208 weeks (depending on the patient)

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 8 (see Table 2), male, 22.3 years old (age at report), 12.5 years (duration of treatment), 8 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

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

CaseNotHPOFreeText: Shunt placement, psychiatric problems

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.793G>C (p.G265R)

Variant1ClinVarID: 638074

Variant1CAID: CA2802098

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

Variant2ClinVarID: 167190

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 44, Poland

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.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 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#: 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: G265R

Variant1ClinVarID: 638074

Variant1CAID: CA2802098

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient 34 (Table 3)

DiseaseAssertion: Attenuated naïve MPS 1

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3 nmol/h/mg per DBS (dried blood spots) determined during NBS.

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.24C>A (p.Ser16_Ala19del)

Variant1ClinVarID: 92638

Variant1CAID: CA145878

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

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: male, 23 year olds (age at report), progressive impairment in ability to perform in school.

DiseaseAssertion: MPS I-H/S

FamilyInfo: N/A

CasePresentingHPOs: Mental deterioration (HP:0001268)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - the patient had been treated with intravenous rhIDU for 13 years before IT rhIDU and had not undergone HSCT. The patient was also enrolled concurrently in an IRB approved non‐interventional longitudinal study of brain structure and function in MPS at the University of Minnesota. He showed stable or improved neurocognitive outcomes after 24 months of IT rhIDU. The patient showed the greatest improvement in his ability to encode verbal stimuli, moving from significantly impaired to the average level. This was accompanied by a significant improvement in adaptive behavior and an improvement to an above average level, in his ability to remember verbal material in a context. Nonverbal memory, both encoding and recall increased although those scores remained below the average range. A baseline of average IQ and attention performance also somewhat improved.

CaseBMT: No

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

Variant1ClinVarID: 167190

Variant1CAID: CA234128

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

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: IL-5b ID number, Table S1.1 of Supplementary Material. Additional PHI not provided.

DiseaseAssertion: Attenuated MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 1211 fmol/punch

CaseERT: N/A

CaseBMT: N/A

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

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

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Anthropometric features

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

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

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

CaseBMT: No

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

Variant1ClinVarID: 11909

Variant1CAID: CA204563

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

Variant2ClinVarID: 638074

Variant2CAID: CA2802098

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A