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#:13-year-old female

DiseaseAssertion: MPS1

FamilyInfo: Healthy, unrelated parents with no family history of MPS ..

ParentalTesting: NR

CasePresentingHPOs:HP:0004322, HP:0002970, HP:0000316, HP:0000286, HP:0007481, HP:0002967, HP:0034337, HP:0001634

CaseHPOFreeText: Inability to extend fingers in both hands, restricted extension of both upper limbs, hyperopia, small jaw, widened intercostal spaces, limited abduction of both upper limbs, Breasts: Tanner stage I. Pubic hair: Tanner stage I, ’’paddle-shaped” sternum, bone age consistently with approximately 8 years,

CaseNotHPOs: HP:0011369,

CaseNotHPOFreeText: Physical examination of the heart, lungs, and abdomen revealed no significant abnormalities. Neurological examinations showed no positive findings.Cortisol, total type I collagen N-terminal propeptide, and adrenocorticotropic hormone (ACTH) levels were all within normal ranges, peripheral blood chromosome karyotype analysis 46, XX.Transabdominal ultrasound of the uterus and bilateral adnexa showed no uterine structure visible. No significant abnormalities in thoracic vertebral bodies.

CasePreviousTesting: NR

Genotyping Method: Whole-exome sequencing and Sanger sequencing

FunctionalAnalysis: Reduced α-L-iduronidase activity - 0.3 nmol/(g·min).

CaseUrineGAGs: NR

CaseERT: No

CaseBMT: No

Variant 1: NM_000203.5(IDUA):c.612_615dup (p.Ser206fs)

Variant 1 ClinVar : 226413

Variant 1 CAID 1: CA10576338

Variant 1 gnomAD : NR