BACKGROUND Glycogen storage disease (GSD) Ia, caused by mutations in the glucose-6-phosphatase (G6PC) gene, is characterized by hepatomegaly, hypoglycemia, lactic acidosis, dyslipidemia, and hyperuricemia. This study aimed to investigate clinical and molecular features and late complications in Korean patients with GSD Ia. RESULTS Fifty-four Korean patients (33 males and 21 females) from 47 unrelated families, who were diagnosed with GSD Ia, based on genetic and biochemical data, between 1999 and 2017, were included in this study. The median age at diagnosis was 3.9 years (range: 5 months to 42 years), and the follow-up period was 8.0 ± 6.8 years. Most patients presented with hepatomegaly during infancy, but hypoglycemic symptoms were not predominant. Genetic analysis showed that all the patients had at least one c.648G > T allele. Homozygous c.648G > T mutations in the G6PC gene were identified in 34 families (72.3%), and compound heterozygotes with c.648G > T were found in the other families. The allele frequency of c.648G > T was 86.2% (81/94), and p.F51S, p.R83H, p.G122D, p.Y128*, p.G222R, and p.T255A were identified. Of 26 adult patients, 14 had multiple hepatic adenomas, and two were diagnosed with hepatocellular carcinoma. Thirteen patients showed renal complications, and seven patients presented gout, despite preventive allopurinol treatment. Twelve patients had osteoporosis, and two patients had pulmonary hypertension. The final heights were 157.9 cm (standard deviation score: - 3.1) in males and 157.8 cm (standard deviation score: - 0.6) in females. CONCLUSION In our Korean patients with GSD Ia, the most common mutation in the G6PC gene was c.648G > T, suggesting a founder effect. Because of only mild hypoglycemia, the patients tended to be diagnosed late. Thus, adult patients with GSD Ia eventually developed diverse and serious complications, which indicates a need for careful monitoring and proper management of this disease.

中文翻译：

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c.648G > T G6PC 基因突变在韩国 Ia 型糖原贮积病患者中占主导地位和晚期并发症。

背景技术由葡萄糖-6-磷酸酶(G6PC)基因突变引起的糖原贮积病(GSD) Ia以肝肿大、低血糖、乳酸酸中毒、血脂异常和高尿酸血症为特征。本研究旨在调查韩国 GSD Ia 患者的临床和分子特征以及晚期并发症。结果 本研究纳入了 1999 年至 2017 年间根据遗传和生化数据诊断为 GSD Ia 的 47 个无关家庭的 54 名韩国患者（33 名男性和 21 名女性）。诊断时的中位年龄为 3.9 岁（范围：5 个月至 42 岁），随访时间为 8.0 ± 6.8 年。大多数患者在婴儿期出现肝肿大，但低血糖症状并不突出。遗传分析显示，所有患者均具有至少一个c.648G > T等位基因。G6PC基因c.648G>T纯合突变在34个家系中发现（72.3%），在其他家系中发现c.648G>T复合杂合子。c.648G > T的等位基因频率为86.2%（81/94），鉴定出p.F51S、p.R83H、p.G122D、p.Y128*、p.G222R和p.T255A。在 26 名成年患者中，14 人患有多发性肝腺瘤，2 人被诊断为肝细胞癌。尽管进行了预防性别嘌醇治疗，13 名患者出现肾脏并发症，7 名患者出现痛风。12名患者患有骨质疏松症，2名患者患有肺动脉高压。男性的最终身高为 157.9 厘米（标准偏差得分：- 3.1），女性为 157.8 厘米（标准偏差得分：- 0.6）。结论 在我们的韩国 GSD Ia 患者中，最常见的 G6PC 基因突变是 c.648G > T，暗示创始人效应。由于仅有轻度低血糖，患者往往被诊断较晚。因此，患有 GSD Ia 的成年患者最终会出现多种严重的并发症，这表明需要仔细监测和适当管理这种疾病。