SLC37A4基因突变致严重高甘油三酯血症的婴儿糖原累积病Ib型1例并文献复习

Glycogen storage disease type Ⅰb with severe hypertriglyceridemia due to SLC37A4 gene mutation: A case report and literature review

目的探讨SLC37A4基因突变致血甘油三酯严重增高的婴儿糖原累积病Ⅰb型(GSDⅠb)的临床特征及其遗传学特征,为临床诊治提供参考。方法报告1例GSDⅠb婴儿的临床表现、实验室检查、影像学检查、治疗和基因突变特点,并行文献复习。结果女,8月龄,因“少食2月,发热1周”就诊,入院后表现为严重高甘油三酯血症(79.97 mmol·L^-1)、难以纠正的反复低血糖、高乳酸血症和肝脏肿大。患儿于我院行血浆置换降脂治疗2次后血甘油三酯显著降低。经鼻胃管泵入脱脂奶,同时添加玉米生淀粉维持血糖稳定,患儿病情逐渐平稳。基因检测结果显示,患儿存在SLC37A4基因杂合变异c.1063G>T(p.E355*)和c.343G>A(p.G115R),分别来自母亲(杂合状态)和父亲(杂合状态)。检索PubMed、万方和中国知网数据库,共筛选到25篇文献,与本文合并后共报道88例GSDⅠb患儿。婴儿期起病45例(51.1%)。临床表现以肝肿大(87.5%)、中性粒细胞减少(81.8%)、高甘油三酯血症(71.6%)、高乳酸血症(69.3%)和低血糖(55.7%)多见,合并症以高尿酸血症(40.9%)、矮小(33.0%)、炎症性肠病(14.8%)和肝腺瘤(14.8%)多见。行肝穿刺活检20例(22.7%)。共报道92个突变位点,包括错义突变、框架移位突变、缺失突变、插入突变、无义突变。中国人种中c.572C>T(p.Pro191leu)最常见(15/57,,26.3%),且仅在中国人种中被检出。结论患儿表现为严重高甘油三酯血症、反复低血糖、高乳酸和肝肿大时,应高度怀疑GSD,基因检查能明确诊断。血浆置换治疗是降低GSDⅠb型患儿严重高甘油三酯血症快速有效的方法,同时应给予脱脂奶粉、玉米生淀粉喂养以维持血脂、血糖水平。

Objective To analyze the clinical presentation and treatment of a case of glycogen storage disease(GSD) type Ⅰb with severe hypertriglyceridemia due to SLC37 A4 gene mutation. Methods The clinical manifestations, laboratory examination, imaging examination, gene mutation characteristics and treatment of an infant with GSD type Ⅰb were concluded. And the related literature was reviewed. Results An eight-month-old female infant was hospitalized for reduced eating for 2 months and fever for 1 week who presented with severe hypertriglyceridemia(triglycerides were 79.97 mmol·L^-1), refractory hypoglycemia, hyperlacticemia, and hepatomegaly. After twice plasmapheresis, triglyceride dropped markedly. After pumped skimmed milk via nasogastric tube and fed with uncooked cornstarch to maintain normoglycemia, the infant’s vital signs became stable. The diagnosis of GSD type Ⅰb was confirmed by molecular genetic testing. Mutation of c.1063 G>T(p.E355*) and c.343 G>A(p.G115 R) were detected in SLC37 A4 gene in this infant, which were separately inherited from her mother and father. Conclusion Glycogen storage disease should be highly suspected in patients with severe hypertriglyceridemia, recurrent hypoglycemia, hepatomegaly. Gene analysis can help to clarify a diagnosis. Plasmapheresis is an effective therapeutic tool to rapidly reduce triglycerides levels in patients with severe hypertriglyceridemia. As for these patients, diet therapy is also demanded such as skimmed milk and uncooked cornstarch.