4例以血细胞减少发病的早发型甲基丙二酸血症

Diagnosis and treatment of 4 cases of early-onset methylmalonic acidemia caused by hemocytopenia

目的 分析4例以血细胞减少为主的甲基丙二酸血症(MMA)的临床特点,提高基层医生对该病的早期识别及临床诊治水平。方法 回顾性分析2019年2月至2021年5月甘肃省妇幼保健院PICU收治的4例以血细胞减少为主要表现的MMA患儿临床资料。结果 4例患儿首发症状均为血细胞减少,经基因检测明确诊断为MMA,临床表现以喂养困难、精神欠佳、反复感染为主。血丙酰肉碱、丙酰肉碱/乙酰肉碱、丙酰肉碱/游离肉碱及尿甲基丙二酸、甲基枸橼酸水平除1例未检测外其余均升高。基因检测提示均为MMACHC基因复合杂合变异,检出的5种变异位点中c.445T>C变异位点未见文献报道,其余4种为已知致病变异。4例患儿中3例患儿死亡,1例患儿经治疗后症状好转,但存在运动发育迟缓。结论 以血细胞减少发病的早发型MMA,临床表现复杂,容易误诊。对于这类疾病,应提高认识,早诊断,早治疗,从而改善患儿预后。

Objective To analyze the clinical characteristics of 4 cases of methylmalonic acidemia(MMA) mainly characterized by hemocytopenia, so as to improve the early recognition and clinical diagnosis and treatment of the disease by grass-roots doctors. Methods The clinical data of 4 patients with MMA admitted to the PICU of Gansu Maternal and Child Health Hospital from February 2019 to May 2021. Results All four children developed with hemocytopenia and were clearly diagnosed as Cb1C MMA by genetic testing. In three children, trilines, progressive platelets, repeated decline in one child,mainly red lines, and the clinical manifestations were mainly feeding difficulties, poor spirit and repeated infection. The levels of blood acetylcarnitine, acetylcarnitine/acetylcarnitine, acetylcarnitine/free carnitine, urine methylmalmalic acid and methyl citrate were increased except in one case not detected due to misdiagnosis. Genetic testing tips were all compound heterozygous variants of the MMACHC gene. The c.445T>C variant loci among the five variant loci were not reported in the literature. The remaining 4 species were known pathogenic variants. Three of the four children died, all clinically showed reduced hemocytic triplet, thrombocytopenia, early onset and poor prognosis, one child with reduced erythroid symptoms improved after treatment, but had motor retardation. Conclusion The first symptom is a high rate of misdiagnosis and easy to delay treatment, Especially, children with thrombocytopenia have a critical condition and a very poor prognosis, for children with hemcytopenia in infancy, ideas should be expanded, and early diagnosis and treatment are key to improving the prognosis of methylmalinaemia.