一例PDHA1突变致女婴丙酮酸脱氢酶E1α缺乏症临床及遗传学分析并文献复习

Clinical and genetic analysis of a girl infant with pyruvate dehydrogenase E1 α deficiency caused by PDHA1 mutation and literature review

目的探讨丙酮酸脱氢酶E1α缺乏症的临床特征及基因突变遗传学特点。方法回顾性分析由河北省人民医院确诊的1例丙酮酸脱氢酶E1α缺乏症罕见女婴患儿的临床特点及基因学特征,并结合本病的研究进展做文献复习。结果罕见女婴发病,起病早,重度精神运动发育落后,持续高乳酸、高丙酮酸血症,代谢性酸中毒,头颅MRI显示透明隔较小,隔间腔缺如;穹隆显示不明确,胼胝体压部细小,呈蓬状向前突。第三脑室顶向背侧抬高,左侧侧脑室扩张向右侧突,左侧室间孔明显扩大。脑电图间歇期:左侧后头部(O1、T5)导联可见大量中高幅棘慢波、慢波,少量多棘慢波散发或连续发放。双侧半球各导联可见大量低幅慢波活动。二代基因测序发现患儿PDHA1基因在chrX-19371287位置有C>T(p.A169V)的杂合错义突变,父母PDHA1基因未见该突变。确诊为丙酮酸脱氢酶E1α缺乏症。结论PDHA1突变所致的丙酮酸脱氢酶E1α缺乏症在早期缺乏特异性表现,且女性患者因有X染色体随机失活,更为少见。对原因不明的精神运动发育落后、持续高乳酸血症、难以纠正的代谢性酸中毒患儿,需警惕该病。可通过基因分析诊断。

Objective To explore the clinical characteristics and genetic characteristics of gene mutation of pyruvate dehydrogenase E1αdeficiency.Methods The clinical and genetic characteristics of a rare girl infant with pyruvate dehydrogenase E1αdeficiency confirmed by Hebei General Hospital were retrospectively analyzed,and the literature was reviewed combined with the research progress of the disease.Results The rare case of baby girl,early onset,psychomotor development is severely backward,persistent hyperlactic acid and hyperpyruvemia,metabolic acidosis,the head MRI shows septum pellucidum is small,interventricular septum is absent;fornix is unclear,splenium of corpus callosum is small and extruded forward like a canopy.The top of the third ventricle is elevated to the dorsal side,the left paracele enlarge to the right,the left interventricular foramen is obviously enlarged.Intermittent periods EEG:a large number of medium and high amplitude spike slow waves,slow waves,and a small amount of multiple spike slow waves are scattered or continuously distributed in the left posterior head(O1,T5).A large amount of low amplitude slow wave can be seen in the bilateral hemisphere.The second-generation gene sequencing found a heterozygous missense mutation of C>T(p.A169v)in the position of chrx-19371287 in the PDHA1 gene of the child,but not in the parent PDHA1 gene.And the diagnosis of pyruvate dehydrogenase E1αdeficiency was identifie.Conclusion PDHAl mutation-induced pyruvate dehydrogenase E1αdeficiency lacks specificity at an early stage,and female patients are more rare due to random inactivation of the X chromosome.It is necessary to be vigilant against metabolic acidosis in children with unexplained psychomotor retardation,persistent hyperlactemia and difficult to correct.It can be diagnosed by gene analysis.