中链酰基辅酶A脱氢酶缺乏症4例患儿的临床特点及ACADM基因变异分析

Analysis of clinical characteristics and ACADM gene variants in four children with Medium chain acyl-CoA dehydrogenase deficiency

目的探讨4例中链酰基辅酶A脱氢酶缺乏症(MCADD)患儿的临床及遗传学特点。方法对2019年8月至2021年8月就诊于郑州大学附属儿童医院、经血氨基酸及酯酰肉碱谱检测和全外显子组测序确诊的4例MCADD患儿进行分析。结果4例患儿均已发病,血氨基酸及酯酰肉碱谱检测辛酰肉碱(C8)浓度均显著升高,主要临床表现为精神反应差3例、间断腹泻伴腹痛1例、呕吐1例、转氨酶升高3例、代谢性酸中毒2例。基因测序共发现5处变异,包括3处错义变异、1处移码变异以及1处剪接变异,其中c.341A>G(p.Y114C)既往未见报道。结论MCADD临床异质性明显,全外显子组测序可协助诊断。了解该病的临床症状及基因变异特点,有助于尽早诊断和治疗。

Objective To explore the clinical and genetic characteristics of four patients with medium-chain acyl-CoA dehydrogenase deficiency(MCADD).Methods Four children who had presented at the Children′s Hospital Affiliated to Zhengzhou University between August 2019 and August 2021 were selected as the study subjects.Clinical data of the children were collected.The children were subjected to whole exome sequencing(WES).Results All of the four children were diagnosed with MCADD.Blood amino acid and ester acyl carnitine spectrum test showed that the concentration of octanoyl carnitine(C8)was significantly increased.The main clinical manifestations included poor mental response(3 cases),intermittent diarrhea with abdominal pain(1 case),vomiting(1 case),increased transaminase(3 cases),and metabolic acidosis(2 cases).Five variants were identified by genetic testing,among which c.341A>G(p.Y114C)was unreported previously.Three were missense variants,one was frameshift variant and one was splicing variant.Conclusion The clinical heterogeneity of MCADD is obvious,and the severity of the disease may vary.WES can assist with the diagnosis.Delineation of the clinical symptoms and genetic characteristics of the disease can facilitate early diagnosis and treatment of the disease.