1例亚硫酸盐氧化酶缺乏症患儿的临床与SUOX基因变异分析

Clinical and genetic analysis of SUOX gene variant in a Chinese patient with isolated sulfite oxidase deficiency

目的探讨亚硫酸盐氧化酶缺乏症(ISOD)患儿的临床表现、生化特征和基因型特点。方法收集先证者及父母的外周血样进行全基因检测,并用Sanger测序对先证者及父母的突变位点进行验证。结果先证者生后27天起病,以发作性抽搐、肌张力障碍及发育落后为主要临床表现,血同型半胱氨酸降低,尿S磺酸半胱氨酸升高,SUOX基因检出了致病的复合杂合突变,即NM_001032386.2:c.68C>G(p.Ser23Ter)和NM_001032386.2:c.650G>A(p.Arg217Gln),根据ACMG/AMP标准和指南被归类为致病性变异。给予限制含硫氨酸饮食,服用甜菜碱、维生素B1治疗,患儿未再出现惊厥发作,但肌张力仍高,精神运动发育无改善,随访至1岁,仍竖头不稳。结论本研究分析了亚硫酸盐氧化酶缺乏症患儿的临床表现、生化特征和基因型特点,扩展了SUOX基因突变谱。

Objective To explore the clinical,laboratory and genetic characteristics of a Chinese patient with isolated sulfite oxidase deficiency(ISOD).Methods Whole genome and Sanger sequencing for blood of the patient and his parents were facilitated as an accurate diagnosis.Results The proband’s main clinical manifestations are paroxysmal convulsion,dystonia and mental retardation at the age of 27 days.Low homocysteine was detected in the plasma.S-sulfocysteine was abnormally elevated in urine.A novel maternal nonsense variant c.68C>G(p.Ser23Ter)and a paternal missense variant c.650G>A(p.Arg217Gln)in SUOX were identified in this case.According to the ACMG/AMP guidelines,the pathogenicity level of novel variants was annotated.Dietary restriction intake of sulfur-containing amino acid,oral betaine and vitamin B1.After 1 year follow-up,the patient had been free of convulsions,axial dystonia were observed,psychomotor development did not improve,and still unstable upright his head.Conclusion This study analyzed the clinical characteristics,biochemical indexes and genotype characteristics of patient with ISOD.The report of ISOD case enriched the mutation spectrum of the SUOX gene.