Inherited Metabolic Diseases, Evelina London Children's Hospital, London, SE1 7EH, UK.
WellChild Laboratory, Evelina London Children's Hospital, London, UK.
Orphanet J Rare Dis. 2022 May 12;17(1):195. doi: 10.1186/s13023-022-02345-2.
Glycogen storage disease type Ib (GSD Ib) is a severe disorder of carbohydrate metabolism due to bi-allelic variants in SLC37A4. It is associated with neutropaenia and neutrophil dysfunction, which has recently been attributed to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5AG6P) within neutrophils. Treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin, is a novel therapy that reduces 1,5-anhydroglucitol (1,5AG) in plasma.
We report our experience in treating 8 paediatric GSD Ib patients with empagliflozin with a cumulative treatment time greater than 12 years. Treatment with a median dose of 5 mg (0.22 mg/kg height weight) of empagliflozin resulted in improvement in bowel health, growth, and laboratory parameters. Plasma 1,5AG levels reduced by a median of 78%. Baseline 1,5AG levels in our cohort were higher than in adult patients with GSD Ib. Hypoglycaemia on empagliflozin treatment occurred in 50% of our cohort.
We report the largest single centre cohort of GSD Ib patients treated with empagliflozin to date. Treatment with SGLT2 inhibitors is a novel and favourable treatment option for neutropaenia and neutrophil dysfunction in GSD Ib. We suggest a low starting dose of empagliflozin with careful titration due to the risk of hypoglycaemia. The interpretation of 1,5AG levels and their role in treatment monitoring is yet to be established, and requires ongoing research.
糖原贮积病 Ib 型（GSD Ib）是一种严重的碳水化合物代谢紊乱，由于 SLC37A4 的双等位基因突变引起。它与中性粒细胞减少症和中性粒细胞功能障碍有关，最近归因于 1,5-脱水葡萄糖-6-磷酸（1,5AG6P）在中性粒细胞内的积累。钠-葡萄糖共转运蛋白-2（SGLT2）抑制剂，如恩格列净的治疗，是一种新的治疗方法，可降低血浆中的 1,5-脱水葡萄糖（1,5AG）。
我们报告了我们用恩格列净治疗 8 例小儿 GSD Ib 患者的经验，累积治疗时间超过 12 年。以 5 毫克（0.22 毫克/公斤身高体重）的中位数剂量使用恩格列净治疗，导致肠道健康、生长和实验室参数改善。血浆 1,5AG 水平中位数降低了 78%。我们队列中的基线 1,5AG 水平高于成人 GSD Ib 患者。我们队列中有 50%的患者在恩格列净治疗时发生低血糖。
我们报告了迄今为止使用恩格列净治疗 GSD Ib 患者的最大单一中心队列。SGLT2 抑制剂的治疗是 GSD Ib 中性粒细胞减少症和中性粒细胞功能障碍的一种新的、有利的治疗选择。由于低血糖的风险，我们建议使用低起始剂量的恩格列净，并谨慎滴定。1,5AG 水平的解释及其在治疗监测中的作用尚未确定，需要进一步研究。
