全羧化酶合成酶基因新发突变致以皮肤为首发症状的多种羧化酶缺乏症一例

A case of multiple carboxylase deficiency presenting with skin lesions as the initial symptom induced by a novel mutation in the holocarboxylase synthetase gene

患儿男,3个月12天.自出生后1个月起阴囊、会阴、臀部和肛周部出现边界清楚的皮肤红斑、鳞屑,渐累及口周、腋下、肘部屈侧、腘窝及颈部.入院前3天出现气促,伴哭吵烦躁、呕吐,无发热及咳嗽.人院检查发现有代谢性酸中毒、高乳酸血症、高氨血症、有机酸尿.通过二代测序和Sanger测序验证发现,先证者全羧化酶合成酶基因第9外显子1522处胞嘧啶>胸腺嘧啶(c.1522C>T)和第11外显子1796_1814缺失(c.1796_1814del),其中c.1796_1814del为新发突变,依据美国医学遗传学与基因组学学会指南,该新发突变评级为致病突变.诊断:多种羧化酶缺乏症.经口服生物素治疗后临床症状得到改善,未出现神经系统症状和体征.

A male patient,who was aged 3 months and 12 days,presented with well-circumscribed erythema and scales on the scrotum,perineum,buttocks and perianal region at 1 month after birth.The lesions gradually involved the perioral and axillary regions,flexor aspect of the elbow,popliteal fossa and neck.Shortness of breath,crying,dysphoria and vomiting occurred without fever and cough 3 days before hospitalization.Laboratory examinations at admission showed metabolic acidosis,hyperlactacidemia,hyperammonemia and organic aciduria.Second-generation sequencing and Sanger sequencing of the holocarboxylase synthetase gene revealed a known mutation c.1522C>T in exon 9 and a novel mutation c.1796_1814del in exon 11.According to a guideline from the American College of Medical Genetics and Genomics,this novel mutation was ranked as a pathogenic mutation.The patient was diagnosed as multiple carboxylase deficiency.His clinical symptoms were improved after oral biotin treatment,no neurological symptoms or signs were observed.