Abstract: Background　Hepatic glycogen storage disease（HGSD） is a rare group of hereditary glycometabolism disorders involving the liver.All types of HGSD have similar clinical manifestations.Gene detection has replaced enzymatic diagnosis requiring liver biopsy，provides a reliable basis for the diagnosis，classification and treatment of HGSD.Objective　To study the clinical characteristics and gene mutation in children with HGSD.Methods　Six children diagnosed with HGSD on the basis of clinical manifestations and laboratory examinations were recruited from Department of Pediatrics，the First People's Hospital of Yunnan Province from 2015 to 2018.Next generation sequencing was used to directly sequence the exons of related genes of HGSD and to compare them with the reference sequences to find possible gene mutations.The clinical manifestations，signs，laboratory results，gene test results，treatment and prognosis of the children were summarized.Results　Hepatomegaly，hypoglycemia，and increased ALT，triacylglyceroll and actic acid were found in all cases，elevated uric acid in 4 cases，and elevated cholesterol in 2 cases.Urinary protein was found in 4 cases.Positive urine ketones and suspected positive urine ketones were found in 4 cases，1 case，respectively.Four cases had short stature.Three cases were found with G6PC mutations，and 2 of them had c.648G>T homozygous mutations，the other 1 had c.262 delG/ c.648 G>T compound heterozygous mutations，but all of them were diagnosed with HGSD type Ⅰa.One case did not undergo the gene testing due to death，but her parents were detected with a heterozygous mutation of G6PC gene，c.49delCinsGTA and c.262delG，respectively，suggesting that she had HGSD type Ⅰa.One case was detected with SLC37A4 gene compound heterozygous mutations：c.1109G>A/c.572C>T，and was diagnosed with HGSD type Ⅰb.Homozygous mutation of c.579delC in AGL gene was detected in 1 case and confirmed as HGSD typeⅢ.Conclusion　This group of HGSD patients had hepatomegaly，hypoglycemia，hyperlipidemia and elevated ALT，generally accompanied by high lactic academia，hyperuricemia，positive urinary ketones and short stature.HGSD type Ⅰa was the most common type（4 cases），and the G6PC mutation type was c.648G > T，c.262delG mutation；1 case was GSD typeⅠb.SLC37A4 c.572C > T mutation is a common mutation in Chinese，but c.1109G > A mutation is newly discovered.One case had HGSD type Ⅲ，with c.579delC mutation of AGL gene as a known pathogenic mutation.

Key words: Liver glycogen storage disease, Glycogen storage disease type Ⅰ, Glucose-6-phosphatase, Glycose-6-phosphate translocase, Glycogen storage disease type Ⅲ, Glycogen debrancher deficiency, Mutation

摘要： 背景　肝糖原累积病是一组罕见的累及肝脏的遗传性糖代谢障碍疾病，各型有相似的临床表现，基因检测已取代有创性肝穿刺酶活性检测的确诊方法，对肝糖原累积病的确诊、分型及治疗提供了可靠的依据。目的　研究肝糖原累积病患儿的临床特点及基因突变情况。方法　选择2015—2018年云南省第一人民医院儿科确诊的6例肝糖原累积病患儿为研究对象。根据临床表现、实验室检查，6例患儿临床诊断为肝糖原累积病，采用二代测序法（NGS）对糖原累积病（GSD）相关基因外显子区直接测序与参考序列进行比较，从而发现可能存在的基因突变。对6例患儿的临床表现、体征及实验室检查结果，基因检测结果，治疗及预后情况进行总结。结果　6例患儿均有肝脏肿大、低血糖、丙氨酸氨基转移酶升高、三酰甘油升高、乳酸升高，尿酸升高4例，胆固醇升高2例。尿蛋白阳性4例，尿酮体阳性4例，1例酮体可疑阳性。4例矮小。3例患儿存在G6PC突变，其中2例为c.648G>T纯合突变，1例为c.262delG/c.648G>T复合杂合突变，均可确诊为GSDⅠa型。1例患儿因已死亡不能行基因检测，其父母分别检出G6PC基因的一个杂合突变：c.49delCinsGGTA、c.262delG，推断患儿为GSDⅠa型。1例患儿检出SLC37A4基因复合杂合突变：c.1109G>A/c.572C>T，确诊为GSDⅠb型。1例患儿检出AGL基因 c.579delC纯合突变，确诊为GSDⅢ型。结论　本组6例肝糖原累积病患儿均有肝肿大、低血糖、高脂血症及丙氨酸氨基转移酶升高，普遍伴有高乳酸、高尿酸、尿酮体阳性及身材矮小。GSDⅠa型最多见，共4例，G6PC突变类型为c.648G>T、c.262delG突变；GSDⅠb型1例，SLC37A4 c.572C>T突变是已知中国人常见突变，c.1109G>A为新发现突变；GSDⅢ型1例，AGL基因c.579delC突变为已知致病突变。

关键词: 肝糖原累积病, 糖原累积病Ⅰ型, 葡萄糖-6-磷酸酶, 葡萄糖-6-磷酸酶转移酶, 糖原累积病Ⅲ型, 糖原脱枝酶, 突变