糖原累积病Ⅵ型和Ⅸa型7例病例报告并文献复习

目的总结糖原累积病(GSD)Ⅵ、Ⅸa型的临床、病理和基因突变情况,提高临床对这两型GSD的认识。方法回顾性收集GSD3例Ⅵ型和4例Ⅸa型患儿的临床资料。结果 (1)7例患儿均为男性,确诊年龄2岁3月至5岁。7例均有肝脏肿大和转氨酶升高,身材矮小1例,空腹低血糖、高乳酸血症和高甘油三酯血症各2例,血酮体增高3例,尿有机酸分析结果阳性2例。7例患儿均有肝细胞弥漫性肿大变形和糖原凝聚,4例有肝脏脂肪变性;3例GSDⅥ型有门管区纤维化、肝硬化表现。3例GSDⅥ型检测到6种PYGL基因突变,c.772+1GA、c.244-1GA、c.730CT(p.L244F)、c.2417_2418del TA(p.I806Sfs X9)为新突变,4例GSDⅨa型检测到4种PHKA2基因突变,c.3529CT(p.Q1177X)、c.3574CT(p.Q1196X)为新突变。(2)复习文献共检索到13篇文献,与本文病例合并后共22例Ⅵ型、99例Ⅸa型GSD。肝脏转氨酶增高和肝脏肿大91.9%~100%,有身材矮小18%~23%、空腹低血糖44%~48%、高甘油三酯血症37%~44%、高乳酸血症35%~72%和血酮体增高50%~56%。肝脏活检均可见肝细胞内糖原凝聚,17%有脂肪变性,Ⅵ型25%、Ⅸa型33%检出肝硬化。报道19种PYGL基因突变,多为点突变,剪切位点突变亦较常见,插入突变少见;43种PHKA2基因突变,突变类型多样。结论肝大伴转氨酶升高的患儿需警惕Ⅵ、Ⅸa型GSD;Ⅵ型患儿可早期存在肝硬化,需要进一步随访。

Report of 7 cases of glycogen storage disease type VI and type IXa

ObjectiveTo summarize the clinical, liver biopsy and gene mutation features of glycogen storage disease type Ⅵ and Ⅸa, so as to improve the clinical understanding of the disease.MethodsA retrospective analysis was performed on seven cases' (3 cases of type Ⅵ , 4 cases of type Ⅸa)clinical manifestation, laboratory examination, liver biopsy and gene mutation spectrum.Related literatures of GSDⅥ and Ⅸa were reviewed and the clinical, liver biopsy and genetic features were summarized..Results①All the 7 cases were male and diagnosis age was 2 years 3 months to 5 years.There were 7 cases with hepatomegaly and transaminase elevation, 1 case with short stature, 2 cases with fasting hypoglycemia, 2 cases wtih hypertriglyceridemia and hypertriglyceridemia, 3 cases with blood ketone bodies, 2 cases with positive analysis of urine organic acids;7 patients'liver biopsy revealed diffuse enlargement of hepatocytes with glycogen aggregation, 4 cases with hepatic steatosis;cirrhosis with portal fibrosis was presented in 3 cases of GSD Ⅵ.6 PYGL mutations were detected in 3 patients of type Ⅵ, c.772+1G>A, c.244-1G>A, c.730C>T(p.L244F), c.2417_2418delTA (p.I806SfsX9)were novel, 4 PHKA2 mutations were detected in 4 patients of type Ⅸa, c.3529C>T(p.Q1177X), c.3574C>T(p.Q1196X) were novel.②13 literatures were retrieved, together with the 7 cases in this study, there were 22 cases of GSD Ⅵ and 99 cases of GSDⅨa.Almost all the children had hepatomegaly and transaminase elevation, some patients had short stature, fasting hypoglycemia, hypertriglyceridemia, hypertriglyceridemia and blood ketone bodies.All the patients' liver biopsy revealed glycogen aggregation in hepatocytes , 17% showed hepatic steatosis, liver cirrhosis was presented in 25% of type Ⅵ and 33% of type Ⅸa patients.19 PYGL gene mutations were reported, most were point mutations, splice site mutation was common and insertion mutation was rare.43 PHKA2 gene mutations were reported and the types were variant.ConclusionThe patients with hepatomegaly accompanied by elevated transaminase should be alerted to be with glycogen storage disease type VI or IXa;patients with type VI may have cirrhosis early and require to be further followed-up.