Case#: Case 1, proband was an 8-year-old male of Mexican origin. He was born at 32 weeks gestational age; 3 lbs and 12 oz. He was diagnosed at 1.5 years old.
DiseaseAssertion: MPS1-H
FamilyInfo: Proband came from a consanguineous union (uncle-niece). Case 2 is the proband's sister.
CasePresentingHPOs: Developmental delay, coarse facial features, gastroesophageal reflux, hiatal hernia, umbilical hernia, recurrent otitis media, hepatomegaly, dysostosis multiplex, joint stiffness (HP:0001263, HP:0000280, HP:0002020, HP:0002036, HP:0001537, HP:0000403, HP:0002240, HP:0000943, HP:0001387)
CaseHPOFreeText: He had bilateral moderate to severe hearing loss. He had a normal ophthalmologic examination at 3 years of age, and at age 8 has not developed corneal clouding. He had contractures at the knees as well.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CaseEnzymeAssay: Enzyme analysis on fibroblasts showed 10% residual alpha-l-iduronidase activity and no detectable activity for heparan N-sulfatase.
CaseUrineGAGs: Urinary quantitation of glycosaminoglycans showed 127 mg/g creatinine of uronic acid by the orcinol reaction (nl. 10.7 ± 8.0) and 449 mg/g creatinine by the carbazole reaction (nl. 16.9 ± 9.9), giving a carbazole to orcinol ratio of almost 3, which is indicative of excess heparan sulfate as compared with dermatan sulfate. The electrophoresis which revealed a strong band of heparan sulfate and slightly less chondroitin sulfate was confirmatory of this conclusion. N-sulfated hexosamine was 126 mg/g creatinine (nl. 15.8 ± 12).
CaseERT: He was started on enzyme replacement therapy (ERT) for iduronidase deficiency at age 3 years. However, his severe hyperactivity often precluded therapy as he could not sit still during the infusions, and the intravenous access catheter infiltrated on numerous occasions. Given his mild somatic symptoms, the concurrent diagnosis of Sanfilippo syndrome, a lethal condition, as well as the difficulty his family had with his complex medical care, the decision was made with the family's participation and accord to discontinue ERT and to treat only those problems that would improve his quality of life. He was on ERT for a total of 3 years.
CaseBMT: He was evaluated for a bone marrow transplant but was determined to be ineligible due to his low developmental quotient.
Variant1: c.923T>C (p.L308P)
Variant1ClinVarID: 502243
Variant1CAID: CA2802119
Variant2: c.923T>C (p.L308P)
Variant2ClinVarID: 502243
Variant2CAID: CA2802119
AdditionalVariants: He also had a homozygous variant (c.268G>A) in the SGSH gene, and additionally diagnosed with Sanfilippo syndrome type A.
ParentalGenotype: N/A
PreviouslyPublished N/A