恩格列净治疗糖原贮积病Ⅰb型的短期效果

Short-term efficacy of empagliflozin in children with glycogen storage disease typeⅠb

目的探讨恩格列净治疗糖原贮积病Ⅰb型(GSDⅠb)患儿的短期效果。方法前瞻性开放标签单臂研究。选取2020年12月至2022年12月于北京协和医院儿科就诊的4例基因诊断明确GSDⅠb患儿为研究对象,所有患儿均存在中性粒细胞减少并接受恩格列净治疗,分别于治疗前及治疗后2周、治疗后1、2、3、6、9、12、15个月收集患儿身高、体重;腹痛腹泻、口腔溃疡、感染次数等临床症状;药物治疗情况;中性粒细胞计数变化,评估治疗疗效。应用液相色谱串联质谱法监测血浆中1,5-脱水葡萄糖醇(1,5AG)浓度的变化。并对低血糖、尿路感染等不良反应进行监测。结果4例GSDⅠb患儿开始恩格列净治疗时年龄分别为15、14、4、14岁,随访时间分别为15、15、12、6个月。维持用药剂量范围为0.24~0.39 mg/(kg·d)。所有患儿在用药1~4个月后口腔溃疡得到改善;例2、3、4腹泻及腹痛频率改善时间分别为1、2、3个月。身高、体重不同程度增加,中性粒细胞绝对计数分别由0.84×10^(9)、0.50×10^(9)、0.48×10^(9)、0.48×10^(9)/L升至1.48×10^(9)、3.04×10^(9)、1.10×10^(9)、0.73×10^(9)/L,3例患儿停用粒细胞集落刺激因子,1例患儿减量。2例患儿血浆1,5AG在恩格列净用药后均明显降低(例2由46.3 mg/L下降至9.6 mg/L,例3由56.1 mg/L下降至15.0 mg/L)。4例患儿均未发生低血糖、泌尿系感染、肝肾功能异常等不良反应。结论短期应用观察中恩格列净可改善GSDⅠb患儿口腔溃疡、腹痛腹泻、反复感染症状,增加中性粒细胞计数,降低血浆中1,5AG浓度,未见低血糖、泌尿系感染等不良反应。

Objective To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease typeⅠb(GSDⅠb).Methods In this prospective open-label single-arm study,the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022.All of them were diagnosed by gene sequencing and had neutropenia.These patients received empagliflozin treatment.Their clinical symptoms such as height and weight increase,abdominal pain,diarrhea,oral ulcer,infection times,and drug applications were recorded at 2 weeks,1 month,2 months,3 months,6 months,9 months,12 months,and 15 months after treatment to assess the therapeutic effect.The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1,5-anhydroglucitol(1,5AG)concentration in plasma.At the same time,adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored.Results The 4 patients with GSDⅠb were 15,14,4 and 14 years old,respectively at the beginning of empagliflozin treatment,and were followed up for 15,15,12 and 6 months,respectively.Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d).The frequency of diarrhea and abdominal pain decreased in cases 2,3,and 4 at 1,2 and 3 months of treatment,respectively.Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×10^(9),0.50×10^(9),0.48×10^(9),0.48×10^(9)/L to 1.48×10^(9),3.04×10^(9),1.10×10^(9),0.73×10^(9)/L,respectively.Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient.Plasma 1,5 AG levels in 2 children were significantly decreased after administration of empagliflozin(from 46.3 mg/L to 9.6 mg/L in case 2,and from 56.1 mg/L to 15.0 mg/L in case 3).All 4 patients had no adverse reactions such as hypoglycemia,abnormal liver or kidney function,or urinary system infection.Conclusion In short-term observation,empagliflozin can improve the symptoms of GSDⅠb oral ulcers,abdominal pain,diarrhea,and recurrent infection,also can alleviate neutropenia and decrease 1,5AG concentration in plasma,with favorable safety.