Background

Glycogen storage disease type 0a (GSD 0a), caused by GYS2 mutations, has a broad phenotypic spectrum, mostly associated with hypoglycemia. This disease has been characterized by the inability to store glycogen in the liver, leading to no hepatomegaly. Although the prevention of hypoglycemia has been considered the first therapeutic goal, the long-term complications remain unclear. In addition, few studies summarized clinical or biochemical features or examined genotype-phenotype correlation.

Case presentation

A 4-year-old Japanese boy was admitted to our hospital because of hypoglycemia. We suspected GSD 0a based on recurrent irritability episodes before feeding, fasting ketotic hypoglycemia, postprandial hyperglycemia/hyperlactatemia, and no hepatomegaly. Mutation analyses revealed novel mutations (p.His610fs and deletion of exons 8–10) in the GYS2 gene. At 5 years old, his growth and development are normal. Fasting symptoms and hypoglycemia remain controlled by dietary management.

Review of literature

We summarized the clinical and biochemical features of 33 patients with GSD 0a and 27 different mutations in the GYS2 gene. Nonspecific fasting symptoms (lethargy, drowsiness, nausea, and irritability) were found in 39% of patients, whereas 41% were asymptomatic. All patients had a combination of fasting ketotic hypoglycemia and postprandial hyperglycemia/hyperlactatemia. Hepatomegaly and hepatic steatosis were observed in 12% and 73% of patients. There was no genotype-phenotype correlation in patients with GSD 0a.

Conclusion

This is a clinical report of a Japanese GSD 0a patient with novel GYS2 mutations and a review of cases. As secondary hepatic disorders may occur due to postprandial hyperglycemia, the treatment's ultimate goal is to prevent both hypoglycemia and hyperglycemia.

中文翻译：

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日本 0a 型糖原贮积病患者的新 GYS2 突变

背景

由GYS2突变引起的 0a 型糖原贮积病 (GSD 0a)具有广泛的表型谱，主要与低血糖有关。这种疾病的特点是无法在肝脏中储存糖原，导致没有肝肿大。尽管预防低血糖被认为是首要的治疗目标，但长期并发症仍不清楚。此外，很少有研究总结临床或生化特征或检查基因型-表型相关性。

案例展示

一名4岁的日本男孩因低血糖住进我院。我们怀疑 GSD 0a 基于喂养前反复发作的易怒、空腹酮症低血糖、餐后高血糖/高乳酸血症和无肝肿大。突变分析揭示了GYS2基因中的新突变（p.His610fs 和外显子 8-10 的缺失） 。5岁时，他的生长发育正常。禁食症状和低血糖仍受饮食管理控制。

文献综述

我们总结了 33 例 GSD 0a 和GYS2基因中 27 种不同突变的患者的临床和生化特征。39% 的患者出现非特异性禁食症状（嗜睡、嗜睡、恶心和易怒），而 41% 的患者无症状。所有患者都有空腹酮症低血糖和餐后高血糖/高乳酸血症。在 12% 和 73% 的患者中观察到肝肿大和肝脂肪变性。GSD 0a 患者没有基因型-表型相关性。

结论

这是日本GSD 0a新GYS2突变患者的临床报告和病例回顾。由于餐后高血糖可能会导致继发性肝病，治疗的最终目标是预防低血糖和高血糖。