糖原累积症Ⅸ型12例临床、病理特点及基因突变位点分析

摘要/Abstract

摘要： 目的探讨糖原累积症Ⅸ型(Glycogen storage disease type Ⅸ,GSD Ⅸ)的临床、病理和基因突变特点。方法回顾性分析2015年10月至2017年10月在解放军第三○二医院青少年肝病诊疗与研究中心住院治疗的12例经基因检测确诊为GSD Ⅸ型的患者,总结其临床、病理特点及与基因突变的关系。结果 12例GSD Ⅸ型患者根据基因突变位点的不同分为三类,其中GSD Ⅸa型10例,均为男性,GSD Ⅸb型1例,女性,GSD Ⅸc型1例,女性。发病年龄中位数为2.1岁。所有患者均有肝大和肝功能异常,伴不同程度的低血糖10例,生长发育落后7例,伴有尿酮体阳性6例、高三酰甘油3例、高乳酸4例。12例患者肝脏病理炎症程度均为G1-2,纤维化程度S1-2 8例,S2-3 3例,肝硬化S4 1例。所有的肝脏病理糖原染色阳性。12例患者共检测出13个糖原磷酸化酶激酶基因突变位点,包括11个错义突变,1个缺失突变,1个剪切突变。其中5个为新发现的突变,分别为PHKA2三个:c.3597-3598del (p.F1199fs),c.1039C>T (p.Q347X),c.749C>T (p.s250L);PHKB一个:c.1776+1G>T (splicing);PHKG2一个:c.925 C>T (p.R309W)。经生玉米淀粉口服等干预治疗,患儿症状可减轻。结论肝大并转氨酶异常的患儿需考虑GSD Ⅸ型诊断,确诊及分型依赖于基因检测。GSD Ⅸ型尽早干预可改善预后。

关键词: 糖原累积症Ⅸ型, 磷酸化酶激酶, 病理, 基因突变

Abstract: Objective To analyze the clinical, pathological features and gene mutations of glycogen storage disease type Ⅸ (GSD Ⅸ) for improving clinical understanding of the disease. Methods Data of 12 pediatric patients who had been genetically diagnosed of GSD Ⅸ and hospitalized in our hospital from October 2015 to October 2017 were analyzed retrospectively. Results According to gene mutations, 12 patients were divided into 3 types, including 10 boys diagnosed of GSD Ⅸa, 1 girl diagnosed of GSD Ⅸb and 1 girl diagnosed of GSD Ⅸc. The median onset age was 2.1 years old. All patients had elevated transaminase levels and hepatomegaly (100%, 12/12). Most patients had different degrees of hypoglycemia (83.3%, 10/12) and growth retardation (58.3%, 7/12). Some patients were with positive urine ketone bodies (50%, 6/12), hypertriglyceridemia (25%, 3/12) and hyperlactacidemia (33.3%, 4/12). All patients were with mild inflammation (G1-2) histologically, among which 8 (66.7%) were in S1-2, 3 (25%) were in S2-3, and 1 (8.3%) was in S4. All cases (12/12) were positive stained with periodic acid Schiff reaction. There were 13 phosphorylase kinase (PHK) gene mutations detected in the 12 patients, including 11 missense mutation, 1 deletion mutation and 1 shear mutation. Five novel mutations were identified, including 3 in PHKA2 (p.F1199fs, p.Q347X and p.s250L), 1 in PHKB (c.1776+1G>T) and 1 in PHKG2 (p.R309W). Raw cornstarch therapy could alleviate the symptoms in most of these patients. Conclusion GSD Ⅸ should be considered in pediatric patients with hepatomegaly and elevated transaminase levels. The accurate diagnosis and classification of GSD Ⅸ depend on genetic test. Intervention should be performed as early as possible to improve the prognosis

Key words: Glycogen storage disease type Ⅸ, Phosphorylase kinase, Pathology, Gene mutations

王璞, 董漪, 徐志强, 陈大为, 王福川, 甘雨, 王丽旻, 闫建国, 曹丽丽, 李爱芹, 朱世殊, 张敏. 糖原累积症Ⅸ型12例临床、病理特点及基因突变位点分析[J]. 肝脏, 2018, 23(9): 764-768.

WANG Pu, DONG Yi, XU Zhi-qiang, CHEN Da-wei, WANG Fu-chuan, GAN Yu, WANG Li-min, YAN Jian-guo, CAO Li-li, LI Ai-qin, ZHU Shi-shu,ZHANG Min. Clinical and pathological features and gene mutation analysis in 12 Chinese patients with glycogen storage disease type Ⅸ[J]. Chinese Hepatolgy, 2018, 23(9): 764-768.

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