Department of Pediatrics, Kumamoto University Hospital, Honjo 1-1-1, Kumamoto City, Japan.
Department of Endocrinology, Beppu Hospital, Saifu 1-6-23, Dazaifu City, Japan.
J Med Case Rep. 2021 Feb 16;15(1):75. doi: 10.1186/s13256-020-02658-5.
Glycogen storage disease (GSD) type Ia is a glycogenesis disorder with long-term complications such as hepatomegaly and renal dysfunction and is caused by congenital loss of glucose-6-phosphatase (G6Pase) expression. G6Pase is essential for the final step of gluconeogenesis and glycogenolysis, and its deficiency causes clinical hypoglycemia in the fasting state during infancy. Contrastingly, patients also show blood glucose trends and glucose intolerance similar to those in type II diabetes. Owing to the contrasting presentation of hypoglycemia with glucose intolerance, glucose control in patients remains a challenge, requiring management of both fasting hypoglycemia and post-prandial hyperglycemia.
The patient was a 45-year old Asian (Japanese) woman who showed disease onset at 3 years of age, when hypoglycemia and hepatomegaly were observed, and GDS type Ia was diagnosed by the lack of G6Pase activity. Over the past 45 years, she presented hyperglycemia and dumping syndrome like symptoms (a feeling of fullness, even after eating just a small amount, abdominal cramping, nausea, sweating, flushing, or light-headedness and rapid heartbeat) at 2 hours after food intake. Her liver and kidney dysfunction also worsened over time. Treatment with exercise combined with a sodium-glucose co-transporter 2 inhibitor and an alpha glucosidase inhibitor alleviated her glucose intolerance and dumping syndrome-like symptoms, without increasing hypoglycemic events.
This case suggests SGLT2 inhibitor as a promising candidate for treating glucose intolerance in GSD type Ia without worsening of hypoglycemia.
糖原贮积病（GSD）Ia 型是一种糖生成障碍，长期并发症包括肝肿大和肾功能障碍，由先天性葡萄糖-6-磷酸酶（G6Pase）表达缺失引起。G6Pase 是糖异生和糖原分解的最后一步所必需的，其缺乏会导致婴儿期空腹时出现临床低血糖。相比之下，患者还表现出与 II 型糖尿病相似的血糖趋势和葡萄糖耐量异常。由于低血糖和葡萄糖耐量异常的表现相反，患者的血糖控制仍然是一个挑战，需要同时管理空腹低血糖和餐后高血糖。
患者为 45 岁亚裔（日本人）女性，3 岁时出现疾病发作，表现为低血糖和肝肿大，由于缺乏 G6Pase 活性，诊断为 GSD Ia 型。在过去的 45 年中，她在进食后 2 小时出现高血糖和倾倒综合征样症状（饱腹感，即使只吃少量食物也会有这种感觉，腹部绞痛，恶心，出汗，潮红，或头晕和心跳加速）。随着时间的推移，她的肝肾功能也逐渐恶化。运动联合钠-葡萄糖共转运蛋白 2 抑制剂和α葡萄糖苷酶抑制剂治疗缓解了她的葡萄糖耐量异常和倾倒综合征样症状，而不会增加低血糖事件。
本病例提示 SGLT2 抑制剂可能是治疗 GSD Ia 型葡萄糖耐量异常的有前途的候选药物，而不会加重低血糖。
