Isolated sulfite oxidase deficiency: a founder mutation

Isolated sulfite oxidase deficiency is a rare autosomal recessive inborn error of sulfur metabolism. Clinical features generally include devastating neurologic dysfunction, ectopia lentis, and increased urinary excretion of sulfite, thiosulfate, and -sulfocysteine. Missed diagnosis is not unusual be...

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Bibliographic Details
Published in:Cold Spring Harbor molecular case studies 2020-12, Vol.6 (6), p.a005900
Main Authors: Mhanni, Aizeddin A, Greenberg, Cheryl R, Spriggs, Elizabeth L, Agatep, Ronald, Sisk, Reena Ray, Prasad, Chitra
Format: Article
Language:English
Subjects:
Age
Dimerization
Excretion
Gene deletion
Metabolism
Mutation
Neonates
Oxidase
Phenotypes
Proteins
Rapid Communication
Seizures
Sulfite
Sulfite oxidase
Sulfur
Thiosulfate
Thiosulfates
Uric acid
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Summary:Isolated sulfite oxidase deficiency is a rare autosomal recessive inborn error of sulfur metabolism. Clinical features generally include devastating neurologic dysfunction, ectopia lentis, and increased urinary excretion of sulfite, thiosulfate, and -sulfocysteine. Missed diagnosis is not unusual because of variability in the sensitivity of the urinary sulfite and thiosulfate screening test. We present clinical, biochemical, and molecular data on two unrelated patients with isolated sulfite oxidase deficiency. The two patients belong to an Indigenous genetic isolate in Manitoba, Canada. Both patients (one male and one female, both now deceased) developed neonatal seizures and demonstrated progressive neurodevelopmental delay. Based on increased urinary excretion of sulfite, thiosulfate, and -sulfocysteine and normal serum uric acid levels, sulfite oxidase deficiency was suspected. Both patients have a homozygous 4-bp deletion, 1347-1350delTTGT in the sulfite oxidase gene ( ), predicting a premature termination of the sulfite oxidase protein leading to absence of the carboxy-terminal third portion of the protein. This domain contains most of the contact sites essential for enzyme dimerization. This deletion mutation resulted in sulfite oxidase deficiency with early-onset severe clinical phenotype.
ISSN:2373-2865
2373-2873
DOI:10.1101/mcs.a005900