晚发型硫半胱氨酸尿症1例并文献复习

Late-onset isolated sulfite oxidase deficiency: a case report and literature review

对2021年7月浙江大学医学院附属儿童医院神经内科收治的1例晚发型硫半胱氨酸尿症(ISOD)患儿的临床资料进行回顾性分析,并对既往已报道的15例晚发型ISOD病例进行复习。患儿,女,1岁起病,因"运动倒退伴精神差5 d"就诊,表现为锥体外系症状、运动发育倒退和癫痫发作;尿液亚硫酸盐增高;头颅磁共振成像(MRI)提示双侧苍白球和黑质病变;基因测序提示亚硫酸盐氧化酶(SUOX)基因c.650(exon5)G>A(p.Arg217Gln)纯合错义突变。16例晚发型ISOD中,发病和确诊的中位年龄分别为10.5个月和34.0个月。主要临床表现为肌张力降低(13例),癫痫发作(10例),运动失调(9例)及晶状体异位(6例)。常见头颅MRI特征依次为苍白球改变(11例)、大脑脚黑质病变(5例)及脑萎缩(4例)。14例晚发型ISOD尿亚硫酸盐试验呈阳性。9例存在SUOX基因错义突变。提示头颅MRI累及双侧苍白球、尿液中亚硫酸盐排出增加及SUOX基因错义突变是晚发型ISOD重要诊断线索。

The clinical data of a case with late-onset isolated sulfite oxidase deficiency(ISOD)admitted in the Department of Neurology,Children′s Hospital,Zhejiang University School of Medicine in July 2021 were retrospectively analyzed.Fifteen previously published cases of late-onset ISOD were also reviewed.The patient was a girl,who was hospitalized because of"motor regression with mental retardation for 5 days"at 1 year old.The manifestations of the patient were extrapyramidal symptoms,regression of motor development and seizures.The level of urinary sulfites in the patient was increased.Magnetic resonance imaging(MRI)features were bilateral pallidus and substantia nigra.Gene sequencing suggested a pure missense mutation of the sulfite oxidase(SUOX)gene c.650(exon5)G>A(p.Arg217Gln).In 16 cases of late-onset ISOD,the median age at onset and diagnosis was 10.5 months and 34.0 months,respectively.The common clinical manifestations were hypotonia(13 cases),seizures(10 cases),movement disorders(9 cases),and ectopia lentis(6 cases).The most common brain MRI feature was pallidus changes(11 cases),followed by lesions of substantia nigra(5 cases),and cerebral atrophy(4 cases).Fourteen cases of late-onset ISOD showed a positive urinary sulfite test.The missense mutation of the SUOX gene was found in 9 cases.It suggested that brain MRI involvement of bilateral pallidus,high excretion of urine sulfites and the missense mutation of the SUOX gene were important diagnostic clues for late-onset ISOD.