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Abstract：
BACKGROUND: Glycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay.
METHODS: Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES). WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient\'s father and mother. Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of β-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive. This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation. After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred.
CONCLUSIONS: The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.
METHODS: Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES). WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient\'s father and mother. Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of β-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive. This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation. After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred.
CONCLUSIONS: The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.
摘要：
背景：糖原贮积病（GSD）是一种由于糖原代谢中的遗传障碍而导致的糖原在组织中过度沉积而引起的疾病。糖原贮积病I型(GSD-I)也称为VonGeirk病和葡萄糖-6-磷酸酶缺乏。这种疾病以常染色体隐性方式遗传，两性都会受到影响。主要症状包括低血糖，肝肿大,酸中毒,高脂血症,高尿酸血症,高乳酸血症,凝血障碍和发育迟缓。
方法：这里，我们介绍了一例13岁女性GSDIa合并多发性炎性肝腺瘤的病例.她因肝肿大来到医院,低血糖,和鼻出血。通过临床表现和影像学及实验室检查,我们怀疑患者患有GSDI。最后，通过肝脏病理和全外显子组测序(WES)确诊.WES揭示了一个同义突变,c.648G>T（p。L216=,NM_000151.4),在外显子5和移码突变中，c.262delG（p。Val88Phefs*14,NM_000151.4),在G6PC基因的第2外显子。根据第一代测序的谱系分析结果,从患者的父亲和母亲获得c.648G>T和c.262delG的杂合突变。肝脏病理显示实性结节为肝细胞增生性病变,免疫组化（IHC）结果显示CD34（不完全血管化）阳性表达，肝脏脂肪酸结合蛋白（L-FABP）和C反应蛋白（CRP）在结节肝细胞中的表达和β-catenin和谷氨酰胺合成酶（GS）的阴性表达。这些发现提示多发性炎性肝细胞腺瘤。大部分被PAS-D消化的PAS染色的外周肝细胞呈强阳性。该患者最终被诊断为GSD-Ia合并多发性炎性肝腺瘤，诊断后接受营养治疗，然后接受活体同种异体肝移植。经过14个月的随访，病人恢复得很好,肝功能和血糖水平保持正常，无并发症发生。
结论：患者诊断为GSD-Ia合并多发性炎性肝腺瘤，接受肝移植治疗。对于出现肝肿大的儿童患者，生长迟缓,和实验室测试异常，包括低血糖,高尿酸血症,和高脂血症,应考虑GSD的诊断。基因测序和肝脏病理在GSD的诊断和分型中起着重要作用。
方法：这里，我们介绍了一例13岁女性GSDIa合并多发性炎性肝腺瘤的病例.她因肝肿大来到医院,低血糖,和鼻出血。通过临床表现和影像学及实验室检查,我们怀疑患者患有GSDI。最后，通过肝脏病理和全外显子组测序(WES)确诊.WES揭示了一个同义突变,c.648G>T（p。L216=,NM_000151.4),在外显子5和移码突变中，c.262delG（p。Val88Phefs*14,NM_000151.4),在G6PC基因的第2外显子。根据第一代测序的谱系分析结果,从患者的父亲和母亲获得c.648G>T和c.262delG的杂合突变。肝脏病理显示实性结节为肝细胞增生性病变,免疫组化（IHC）结果显示CD34（不完全血管化）阳性表达，肝脏脂肪酸结合蛋白（L-FABP）和C反应蛋白（CRP）在结节肝细胞中的表达和β-catenin和谷氨酰胺合成酶（GS）的阴性表达。这些发现提示多发性炎性肝细胞腺瘤。大部分被PAS-D消化的PAS染色的外周肝细胞呈强阳性。该患者最终被诊断为GSD-Ia合并多发性炎性肝腺瘤，诊断后接受营养治疗，然后接受活体同种异体肝移植。经过14个月的随访，病人恢复得很好,肝功能和血糖水平保持正常，无并发症发生。
结论：患者诊断为GSD-Ia合并多发性炎性肝腺瘤，接受肝移植治疗。对于出现肝肿大的儿童患者，生长迟缓,和实验室测试异常，包括低血糖,高尿酸血症,和高脂血症,应考虑GSD的诊断。基因测序和肝脏病理在GSD的诊断和分型中起着重要作用。
