新生儿孤立性亚硫酸盐氧化酶缺乏症一例并文献复习

Neonatal isolated sulfite oxidase deficiency:a case report and literature review

目的探讨新生儿孤立性亚硫酸盐氧化酶缺乏症(isolated sulfite oxidase deficiency,ISOD)的临床特征和实验室检查特点。方法对西安市儿童医院新生儿科收治的1例ISOD患儿的临床资料进行回顾性分析,并以"孤立性亚硫酸盐氧化酶缺乏症"、"婴儿,新生"、"isolated sulfite oxidase deficiency"、"SUOX gene"、"infant,newborn"等为检索词,分别对中国知网、万方数据库、国家科技图书文献中心、中国科技论文在线、PubMed、Web of Science、Embase数据库自建库至2021年1月收录的文献进行检索,总结新生儿ISOD的临床和实验室检查特点、治疗及预后。结果本例为足月男婴,表现为眼球运动障碍、顽固性抽搐,伴喂养困难、肌张力增高、发育落后和小头畸形,尿亚硫酸盐试纸试验阳性、尿酸正常,SUOX基因c.475G>T和c.1201A>G复合杂合变异,5月龄头颅MRI见多发软化灶及脑萎缩,8月龄死亡。文献检索共收集29篇32例ISOD患儿,28例(87.5%)于生后1周内发病,32例均有抽搐发作,可伴喂养困难、肌张力改变、发育落后、小头畸形及晶状体异位,实验室检查尿亚硫酸盐、S磺酰半胱氨酸升高,尿酸、黄嘌呤/次黄嘌呤正常,血同型半胱氨酸降低。头颅影像学特征为脑白质囊性变、脑萎缩。23例基因检测存在SUOX基因变异。治疗以对症支持为主,最终死亡15例,13例存活患儿均有药物难治性癫痫和发育落后,4例临床结局未知。结论新生儿ISOD特征表现为顽固性抽搐、喂养困难、发育落后、脑白质囊性变、脑萎缩,尿亚硫酸盐升高、血同型半胱氨酸降低、尿酸正常可作为诊断的重要线索,基因检测有助于早期诊断。

Objective To study the clinical and laboratory characteristics of neonatal isolated sulfite oxidase deficiency(ISOD).Methods An infant with neonatal ISOD admitted to our hospital was retrospectively analyzed.Using key words"isolated sulfite oxidase deficiency","SUOX gene","Infant,newborn",databases including CNKI,Wanfang database,National library and literature center of science and technology,China science paper online,PubMed,Web of Science and EMBASE(up to January 2021)were searched and literature review was conducted.The clinical manifestations,laboratory results,treatment and prognosis were analyzed.Results Our patient was a full-term male infant with eye movement disorder,refractory seizures,feeding difficulties,increased muscle tone,developmental retardation and microcephaly.Urine sulfite paper-strip test was positive.Uric acid was normal.Whole exon sequencing(WES)revealed SUOX c.475G>T and c.1201A>G compound heterozygous mutations.Cranial MRI showed multiple encephalomalacia and brain atrophy at 5-month of age.The infant died at 8-month.In the literature review,a total of 29 articles and 32 cases of neonatal ISOD were found.87.5% of the cases developed symptoms within 1-week after birth.All had convulsive seizures.Some of them had feeding difficulties,muscle tone changes,developmental retardation,microcephaly and ectopia lentis.Cranial imaging showed white matter cystic lesions and brain atrophy.Laboratory examination showed elevated urinary sulfite and S-sulfocysteine.Uric acid and xanthine/hypoxanthine were normal.Blood homocysteine was decreased.23 cases received genetic testing and all of them had SUOX mutations.The treatment was mainly symptomatic relief and supportive treatment.During follow-up,15 cases died,13 cases survived and 4 cases were unknown.All the surviving children had drug-resistant convulsions and developmental retardation.Conclusions Neonatal ISOD may present with refractory convulsions,feeding difficulties and developmental retardation.Cystic white matter changes and brain atrophy may be seen on cranial imaging.Elevated urinary sulfites,decreased blood homocysteine and normal uric acid are important clues for diagnosis.Genetic testing is helpful for early diagnosis.