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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+1G>A、c.244-1G>A、c.730C>T(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.3529C>T(p.Q1177X)、c.3574C>T(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。
Objective To summarize the clinical, pathological and gene mutation status of type Ⅵ and Ⅸ a of glycogen storage disease (GSD), and to improve the clinical understanding of these two types of GSD. Methods The clinical data of 3 cases of GSD type Ⅵ and 4 cases of Ⅸ a type children were retrospectively collected. Results (1) All 7 cases were male and their age at diagnosis was from 2 years old to 5 years old. Seven cases had liver enlargement and elevated transaminases, short stature in 1 case, fasting hypoglycemia, lactic acidosis and hypertriglyceridemia in 2 cases, blood ketone body increased in 3 cases, urine organic acid analysis was positive in 2 cases . All of the 7 children had diffuse enlargement of liver cells and glycogen condensation, 4 cases of hepatic steatosis and 3 cases of portal hyperplasia and cirrhosis in 3 cases. Six kinds of PYGL gene mutations were detected in three cases of GSD Ⅵ type, c.772 + 1G> A, c.244-1G> A, c.730C> T (p.L244F), c.2417_2418del TA (p.I806Sfs X9) Four new mutations of PHKA2 gene were detected in four cases of GSDⅨa, c.3529C> T (p.Q1177X) and c.3574C> T (p.Q1196X) were new mutations. (2) A total of 13 articles were reviewed in reviewing literature. Twenty-two cases of type Ⅵ and 99 cases of type Ⅸ a GSD were merged with the present case. Liver transaminases and enlargement of the liver 91.9% to 100%, short stature 18% to 23%, fasting hypoglycemia 44% to 48%, hypertriglyceridemia 37% to 44%, hyperlactia 35% 72% and blood ketone body increased by 50% to 56%. Hepatic biopsy showed glycogen aggregation in liver cells, 17% had fatty degeneration, Ⅵ type 25%, Ⅸ a type 33% detected cirrhosis. Ninety-nine PYGL mutations were reported, most of them were point mutations. Mutations at cleavage sites were also common, and insertional mutations were rare. Forty-three PHKA2 mutations were found in various types of mutations. Conclusions Children with hepatomegaly and elevated aminotransferases should pay attention to Ⅵ and Ⅸ a GSD. Children with type Ⅵ may have cirrhosis early and need further follow-up.