Introduction: Heterozygous activating mutations in KCNJ11 cause both permanent and transient neonatal diabetes. A minority of patients also have neurological features. Early genetic diagnosis has important therapeutic implications as treatment with sulfonylurea provides good metabolic control and exerts a protective effect on neuromuscular function. Case presentation: A term female infant with normal birth weight (2.73 Kg, z-score: -1.69) was admitted to the Neonatal Unit at Addenbrookes Hospital. She had been antenatally diagnosed with KCNJ11 mutation-R201C inherited from her glibenclamide‐treated mother who continued sulfonylurea treatment throughout pregnancy. A continuous glucose monitoring system inserted at 20 hours of age showed progressive rise of blood glucose concentrations, prompting treatment with glibenclamide on day 2 of life. Initial attempts to treat with an extemporaneous solution of glibenclamide (starting dose 0.2mg/kg/day) resulted in inconsistent response and significant hypoglycaemia and hyperglycaemia. A licensed liquid formulation of glibenclamide (Amglidia) at a starting dose of 0.05 mg/kg/day was used with stabilisation of blood glucose profile within 24 hours. Other than a mild transient elevation in transaminase, treatment was well tolerated. At most recent review (age 12 months), the patient remains well with age-appropriate neurodevelopment. Overall glucose control is reasonable with estimated HbA1c of 7.6% (59.9 mmol/mol). Conclusion: Early post-natal glibenclamide treatment of insulin-naïve patients with KATP-dependent neonatal diabetes is safe, provides good metabolic control and has a potential protective effect on neurological function. The formulation of the medicine needs to be carefully considered in the context of the very small doses required in this age group.


中文翻译：

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产后早期使用格列本脲治疗继发于产前诊断的 KJCN11 突变的永久性新生儿糖尿病

简介：KCNJ11 中的杂合激活突变会导致永久性和短暂性新生儿糖尿病。少数患者也有神经系统特征。早期基因诊断具有重要的治疗意义，因为磺酰脲治疗可提供良好的代谢控制并对神经肌肉功能发挥保护作用。案例介绍：一名出生体重正常的足月女婴（2.73 公斤，z 评分：-1.69）被收入 Addenbrookes 医院的新生儿科。她在产前被诊断出患有 KCNJ11 突变 - R201C，遗传自她接受格列本脲治疗的母亲，她在整个怀孕期间继续接受磺脲类药物治疗。在 20 小时大时插入的连续血糖监测系统显示血糖浓度逐渐升高，促使在出生后第 2 天使用格列本脲进行治疗。最初尝试用格列本脲的临时溶液（起始剂量 0.2mg/kg/天）治疗导致不一致的反应和显着的低血糖和高血糖。使用起始剂量为 0.05 mg/kg/天的经许可的格列本脲 (Amglidia) 液体制剂，可在 24 小时内稳定血糖曲线。除了转氨酶轻度短暂升高外，治疗耐受性良好。在最近的复查中（12 个月大），患者的神经发育状况良好，与年龄相适应。总体血糖控制是合理的，估计 HbA1c 为 7.6% (59.9 mmol/mol)。结论：对于未接受过胰岛素治疗的 KATP 依赖型新生儿糖尿病患者，产后早期格列本脲治疗是安全的，可提供良好的代谢控制，并对神经功能具有潜在的保护作用。