蛋白敏感性低血糖5例病例报道及文献复习

Report of five cases of protein-sensitive hypoglycemia with literature review

目的总结蛋白敏感性低血糖的临床特征、基因突变及治疗随访情况,以提高临床医师对蛋白敏感性低血糖的诊治认识。方法2015年6月至2017年12月在复旦大学附属儿科医院内分泌遗传代谢科收治的5例蛋白敏感性低血糖病例,对其临床表现、蛋白负荷试验以及治疗随访资料进行分析。其中4例进行内分泌遗传代谢疾病基因组合的高通量测序。系统复习国内外蛋白敏感性低血糖文献报道,归纳其临床表现、基因突变及治疗效果。结果在5例蛋白负荷试验确诊蛋白敏感性低血糖的患儿中,谷氨酸脱氢酶1(GLUD1)基因突变3例(c.965G>A,p.R322H:2例;c.943C>T,p.H315Y:1例),L-3-羟酰基-CoA脱氢酶(HADH)基因复合杂合突变1例(c.29G>C,p.R10P;c.89T>A,p.V30E)。5例患儿低蛋白饮食(蛋白质1~1.2g·kg^-1·d^-1)后低血糖发作被明显控制。通过复习文献,共检索到18篇文献,与本文病例合并后共有161例蛋白敏感性低血糖患者,其中GLUD1基因激活突变149例,HADH失活突变10例。结论以“低血糖”就诊的患儿,如伴进食后出现严重的低血糖、伴或不伴高血氨,需注意蛋白敏感性低血糖可能,蛋白负荷试验可以协助诊断。

Objective To summarize the clinical feature,gene mutations,diagnosis,treatment,and followup data of protein-sensitive hypoglycemia,so as to improve the clinical understanding of the disease.Methods Five patients were diagnosed with protein-sensitive hypoglycemia during June in 2015 and December in 2017 from the Department of Pediatric Endocrinology and Inherited Metabolic Diseases,Children's Hospital of Fudan University.Clinical data of 5 cases were summarized,including clinical manifestations,findings of protein sensitivity test,therapy effect and prognosis.The endocrine and metabolic panel was used to investigate the genetic cause of four patients.Related literatures of protein-sensitive hypoglycemia were reviewed,and the phenotypes,genotypes,and therapy effects were summarized.Results Among the 5 patients diagnosed with positive results of protein-sensitive hypoglycemia,three were found to harbor glutamate dehydrogenasel (GLUD1 )mutations (c.965G>A,p.R322H:2 cases;c.943C >T,p.H315Y:1 case),and another one had complex heterozygous mutations in L-3-hydroxyacyl-CoA dehydrogenase (HADH,c.29G>C,p.R10P;c.89T>A,p.V30E).5 patients were euglycemia without any medical support after low protein diet.In 18 literatures retrieved and this study,there were totally 161 cases of protein-sensitive hypoglycemia (149 cases with GLUD1 mutations and 10 cases with HADH mutations).Conclusions When a child was admitted because of hypoglycemia,the diagnosis of protein-sensitive hypoglycemia should be suspected if he or she also had postprandial hypoglycemia,with or without hyperammonemia. the diagnosis of protein-sensitive hypoglycemia.