Case#: Patient 3, male, brother of Patient 7 (see Table 1)

DiseaseAssertion: MPS I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Low IDUA enzyme activity 1.60 (Ref. 4.87 ~ 54.70 μmol/g protein/h)

CaseUrineGAGs: Positive GAG tests

CaseERT: N/A

CaseBMT: N/A

Variant1: c.300-3C>G

Variant1ClinVarID: 551563

Variant1CAID: CA549265042

Variant2: c.1874A>C (p.Y625S)

Variant2ClinVarID: 2910181

Variant2CAID: CA355965961

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 7, female, sister of Patient 3 (see Table 1)

DiseaseAssertion: MPS I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Low IDUA enzyme activity 0.46 (Ref. 4.87 ~ 54.70 μmol/g protein/h)

CaseUrineGAGs: Positive GAG tests

CaseERT: N/A

CaseBMT: N/A

Variant1: c.300-3C>G

Variant1ClinVarID: 551563

Variant1CAID: CA549265042

Variant2: c.1874A>C (p.Y625S)

Variant2ClinVarID: 2910181

Variant2CAID: CA355965961

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: TW1-1 ID number, Table S1.1 of Supplementary Material. Stored Frozen (-20ºC). Other identifying factors N/A

DiseaseAssertion: Severe MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: 301 fmol/punch

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1874A>C (p.Y625S)

Variant1ClinVarID: 2910181

Variant1CAID: CA355965961

Variant2: c.300-3C>G

Variant2ClinVarID: 551563

Variant2CAID: CA549265042

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: MPS I_Case 01, male newborn

DiseaseAssertion: MPS type I, MPS I, MPS-I, attenuated MPS I

FamilyInfo: MPS I_Case 01 and MPS I_Case 05 are siblings

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText: This proband is believed to be an affected MPS-patient however, the proband did not have any obvious clinical symptoms to date (up to two years of age). The paper states that this attenuated MPS I case will need a long term follow up.

CaseEnzymeAssay: Proband identified by newborn screening. alpha-L-iduronidase activity in dried blood spot sample is 0.42 umole/L/Hr; this is below the study’s DBS enzyme activity cutoff value of 3 umol/L/h

CaseUrineGAGs: Urine DMB GAG ratio is 107 mg/mmol creatinine. 10.9 ug/ml dermatan sulfate in urine (<0.41 ug/ml is the reference cutoff for dermatan sulfate in this study). 2.67 ug/ml heparan sulfate in urine (<0.8 ug/ml is the reference cutoff for heparan sulfate in this study). 7/75 ug/ml keratan sulfate in urine.

CaseERT: Don’t know (would assume no since the proband is a newborn)

CaseBMT: Don’t know (would assume no since the proband is a new born)

Variant1: c.300–3C>G

Variant1ClinVarID: 551563

Variant1CAID: CA549265042

Variant2: c.1874A>C, p.Y625S

Variant2ClinVarID: 2910181

Variant2CAID: CA355965961

AdditionalVariants: No additional variants are mentioned

ParentalGenotype: No parental testing results are available

PreviouslyPublished No statement from the author indicating the proband is previously published. Since this is a newborn study, I strongly believe this is the proband’s first time being published.

Case#: MPS I_Case 05, female newborn

DiseaseAssertion: MPS type I, MPS I, MPS-I, attenuated MPS I

FamilyInfo: MPS I_Case 01 and MPS I_Case 05 are siblings

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText: This proband is believed to be an affected MPS-patient however, the proband did not have any obvious clinical symptoms to date (up to two years of age). The paper states that this attenuated MPS I case will need a long term follow up.

CaseEnzymeAssay: Proband identified by newborn screening. alpha-L-iduronidase activity in dried blood spot sample is 0.56 umole/L/Hr; this is below the study's DBS enzyme activity cutoff value of 3 umol/L/h

CaseUrineGAGs: Urine DMB GAG ratio is 65.7 mg/mmol creatinine. 4.76 ug/ml dermatan sulfate in urine (<0.41 ug/ml is the reference cutoff for dermatan sulfate in this study). 3.35 ug/ml heparan sulfate in urine (<0.8 ug/ml is the reference cutoff for heparan sulfate in this study). 0.17 ug/ml keratan sulfate in urine.

CaseERT: Don't know (would assume no since the proband is a newborn)

CaseBMT: Don't know (would assume no since the proband is a newborn)

Variant1: c.300–3C>G

Variant1ClinVarID: 551563

Variant1CAID: CA549265042

Variant2: c.1874A>C, p.Y625S

Variant2ClinVarID: 2910181

Variant2CAID: CA355965961

AdditionalVariants: No additional variants mentioned

ParentalGenotype: No parental testing results are available

PreviouslyPublished No statement from the author indicating the proband is previously published. Since this is a newborn study, I strongly believe this is the proband’s first time being published.

Case#: Infant #8, male.

DiseaseAssertion: MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 1.60 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)

CaseUrineGAGs: DMB/Cre. Ratio - 17.97, DS - 21.18, HS - 11.34, KS - 2.0 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.300-3C>G

Variant1ClinVarID: 551563

Variant1CAID: CA549265042

Variant2: c.1874A>C (p.Y625S)

Variant2ClinVarID: 2910181

Variant2CAID: CA355965961

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Infant #9, female.

DiseaseAssertion: MPS-I

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.46 IDUA enzyme activity (Ref. 5.9–27.8 μmol/g protein/h)

CaseUrineGAGs: DMB/Cre. Ratio - 33.61, DS - 5.91, HS - 9.38, KS - 0.28 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.300-3C>G

Variant1ClinVarID: 551563

Variant1CAID: CA549265042

Variant2: c.1874A>C (p.Y625S)

Variant2ClinVarID: 2910181

Variant2CAID: CA355965961

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Chinese. 12 years old (age at report)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Short stature, macrocephaly, coarse face, corneal clouding, skeletal deformities, hepatosplenomegaly, hearing impairment, tracheal stenosis, hypertrophic cardiomyopathy, obstructive sleep apnea, umbilical hernia, anemia, ichthyosis (HP:0004322, HP:0000256, HP:0000280, HP:0007957, HP:0000924, HP:0001433, HP:0000365, HP:0002777, HP:0001639, HP:0002870, HP:0001537, HP:0001903, HP:0008064

CaseHPOFreeText: Normal intelligence, adenoid hyperplasia, tonsil hypertrophy

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: A very low level of IDUA activity (1.8%) was detected in the patient's fibroblast cells (data not shown).

The effects of both mutations on IDUA activity and/or splicing were examined by transfection into COS-7 cells of the IDUA cDNA construct. When compared to that of wild-type cDNA, 87.5, 1.6, and 0.4% IDUA activity was observed with the IDUA cDNA containing the wild-type acceptor splice site (388-3c), the mutated acceptor splice site (388-3g), or L346R.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1037T>G (p.Leu346Arg)

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.300-3C>G; c.388-3C>G in the paper (old nomenclature)

Variant2ClinVarID: 551563

Variant2CAID: CA549265042

AdditionalVariants: p.Q33H (polymorphism)

ParentalGenotype: Maternal: c.1037T>G (p.L346R); Paternal: c.300-3C>G (c.388-3C>G in the paper, old nomenclature)

PreviouslyPublished N/A

Case#: Patient 43, male, Han origin, 5 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Macrocephaly (HP:0001263, HP:0000256)

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.300-3C>G

Variant1ClinVarID: 551563

Variant1CAID: CA549265042

Variant2: c.530dupT (p.Glu178ArgfsTer5) (Paper refers to the variant as c.531dupT, there is a typo in the article where all duplication variants are one base pair off)

Variant2ClinVarID: N/A

Variant2CAID: CA2586973520

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

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