Weston Paediatric Endocrinology and Diabetes Clinic, Cambridge University Hospital NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK,
Weston Paediatric Endocrinology and Diabetes Clinic, Cambridge University Hospital NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
Horm Res Paediatr. 2022;95(5):476-483. doi: 10.1159/000525989. Epub 2022 Jul 11.
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.
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 h 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 0.2 mg/kg/day) resulted in inconsistent response and significant hypoglycaemia and hyperglycaemia. A licenced liquid formulation of glibenclamide (AMGLIDIA) at a starting dose of 0.05 mg/kg/day was used with stabilization of blood glucose profile within 24 h. 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).
Early postnatal glibenclamide treatment of insulin-naive 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.
KCNJ11 中的杂合激活突变可导致永久性和暂时性新生儿糖尿病。少数患者还有神经学特征。早期基因诊断具有重要的治疗意义，因为磺酰脲类药物治疗可提供良好的代谢控制，并对神经肌肉功能产生保护作用。
一名足月女婴，出生体重正常（2.73kg，z 评分：-1.69），被收入阿登布鲁克医院新生儿病房。她在产前被诊断出患有 KCNJ11 突变-R201C，该突变来自于她接受格列本脲治疗的母亲，其在整个孕期都继续接受磺酰脲类药物治疗。在出生后 20 小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 天开始使用格列本脲治疗。最初尝试使用格列本脲的临时溶液（起始剂量 0.2mg/kg/天）治疗效果不一致，且出现明显低血糖和高血糖。随后使用了一种许可的格列本脲液体制剂（起始剂量 0.05mg/kg/天），在 24 小时内稳定了血糖谱。除了转氨酶短暂轻度升高外，治疗耐受良好。在最近的随访（12 个月龄）时，患者情况良好，神经发育正常。整体血糖控制合理，估计 HbA1c 为 7.6%（59.9mmol/mol）。
对胰岛素初治的 KATP 依赖性新生儿糖尿病患者，在新生儿期早期使用格列本脲治疗是安全的，可提供良好的代谢控制，并可能对神经功能有保护作用。在这个年龄段，需要仔细考虑药物剂型，因为所需剂量非常小。
