1例全羧化酶合成酶缺乏症患儿的临床特征及基因突变分析

Clinical features and genetic analysis of a case with holocarboxylase synthase deficiency

目的分析1例全羧化酶合成酶缺乏症(HLCSD)患儿的临床表现及基因突变特点,以提高临床医师对该疾病的认识。方法回顾性分析1例通过基因检测确诊为HLCSD患儿的临床资料、诊疗过程及遗传学特征。结果男性患儿,6月,临床表现为反复高血糖合并顽固性代谢性酸中毒,经全外显子组测序分析发现HLCS基因的2个尚未报道的变异位点:c.271_c.272delAG(p.Arg91GlyfsX6)、c.1487T>A(p.Ile496Lys),最终确诊为HLCSD,口服生物素治疗后临床症状明显改善。结论对于糖代谢紊乱合并顽固性代谢性酸中毒患儿,应考虑HLCSD可能。血氨基酸和酰基肉碱质谱分析及基因检测可以早期诊断并改善预后。

Objective To analyze the clinical features and genetic characteristics of a child with holocarboxylase synthase deficiency(HLCSD).Methods A retrospective analysis of the clinical data,diagnosis and treatment process,genetic characteristics of a child diagnosed with HLCSD by genetic testing was undertaken.Results The patient,male,6 months old,presented with recurrent hyperglycaemia and refractory metabolic acidosis.Whole exome sequencing analysis revealed two previously unreported genetic variations in the HLCS gene:c.271uc.272delAG(p.Arg91GlyfsX6)and c.1487T>A(p.Ile496Lys).The patient was finally diagnosed with HLCSD and clinical symptoms improved significantly after oral biotin treatment.Conclusion The possibility of HLCSD should be considered in children with impaired glucose metabolism and refractory metabolic acidosis.Mass spectrometry analysis of blood amino acids and acylcarnitine and genetic testing may allow early diagnosis and improve prognosis.