Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba R3A 1S1, Canada.
Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3A 1S1, Canada.
Cold Spring Harb Mol Case Stud. 2020 Dec 17;6(6). doi: 10.1101/mcs.a005900. Print 2020 Dec.
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.
孤立型亚硫酸氧化酶缺乏症是一种罕见的常染色体隐性遗传性硫代谢紊乱。临床特征通常包括毁灭性的神经功能障碍、晶状体异位和亚硫酸盐、硫代硫酸盐和 - 磺基半胱氨酸尿排泄增加。由于尿中亚硫酸盐和硫代硫酸盐筛选试验的敏感性存在差异，漏诊并不罕见。我们介绍了两名孤立型亚硫酸氧化酶缺乏症患者的临床、生化和分子数据。这两名患者来自加拿大马尼托巴省的一个土著遗传隔离群体。两名患者（一男一女，均已去世）均在新生儿期出现癫痫发作，并表现出进行性神经发育迟缓。基于亚硫酸盐、硫代硫酸盐和 - 磺基半胱氨酸尿排泄增加和血清尿酸水平正常，怀疑为亚硫酸氧化酶缺乏症。两名患者均携带亚硫酸氧化酶基因中 4 个碱基缺失（1347-1350delTTGT）的纯合子突变（），导致亚硫酸氧化酶蛋白提前终止，从而缺失蛋白的羧基末端的第三部分。该结构域包含酶二聚化所必需的大多数接触位点。这种缺失突变导致亚硫酸氧化酶缺乏症，具有早发性严重临床表型。
