Imerslund-Grasbeck综合征1例并文献复习

Case report of Imerslund-Gräsbeck syndrome and literature review

对苏州大学附属儿童医院神经内科2018年12月确诊的1例Imerslund-Grasbeck综合征(IGS)患儿的临床表型及基因特征进行回顾性分析,同时进行文献复习。患儿,男,16岁5个月,因"双下肢无力2周"收住入院,既往有巨幼细胞性贫血及孤立性蛋白尿病史。血尿遗传代谢提示甲基丙二酸血症,基因检测发现AMN基因突变:c.742C>T(p.Q248*)及c.761G>A(p.G254E),为复合杂合突变,分别来自其父母,均已被报道。肌内注射羟钴胺和口服甜菜碱治疗后,患儿症状得到改善。结合文献复习发现,AMN基因相关IGS临床多存在巨幼细胞性贫血及孤立性蛋白尿,年龄较大儿童可并运动障碍、痴呆、谵妄等神经系统症状或精神病,该病临床表型多变,易引起误诊。本例患儿表现为轻度可逆性周围神经病的特殊表型,拓展了AMN基因的致病临床表型谱。另外,维生素B_(12)代谢障碍引起的周围神经病变为可逆性损害,建议对病因不明的周围神经病进行维生素B_(12)测定、相关基因检测和维生素B_(12)治疗。

Clinical phenotype and gene characteristics of a patient diagnosed with Imerslund-Gräsbeck syndrome(IGS)in Department of Neurology,Children′s Hospital of Soochow University in December 2018 were analyzed retrospectively,and literature review was conducted.The 16 years and 5 months old boy was admitted to the hospital with symptoms of weakness of lower limbs for 2 weeks.He had a history of megaloblastic anemia and isolated proteinuria.Genetic metabolism of hematuria showed methylmalonic academia.Genetic analysis revealed a compound heterozygous AMN gene mutation[c.742C>T(p.Q248*)and c.761G>A(p.G254E)].These two mutations were derived from his parents respectively,which had been reported before.Symptoms of the patient improved after intramuscular administration of hydroxycobalamin and oral betaine.Review of the literature indicated that the clinical manifestations of AMN gene-related IGS were mostly megaloblastic anemia and isolated proteinuria,and the older children might suffer from neurological symptoms such as movement disorders,dementia,delirium or psychosis.The clinical phenotype of this disease was variable,which might easily lead to misdiagnosis.The patient presented with a special phenotype of mild reversible peripheral neuropathy,which expanded the clinical phenotype of pathogenic genes of AMN gene.In addition,peripheral neuropathy caused by vitamin B_(12) metabolic disorders is reversible,and it is suggested to measure vitamin B_(12),test related genes and treatment with vitamin B_(12) in peripheral neuropathy of unknown etiology.