OBJECTIVE Neonatal diabetes has been shown to be associated with high neuropsychiatric morbidity in a genotype-phenotype-dependent manner. However, the specific impact of different mutations on intellectual functioning is still insufficiently characterized. Specifically, only a small number of subjects with developmental delay have been comprehensively assessed, creating a knowledge gap about patients carrying the heaviest burden. RESEARCH DESIGN AND METHODS We assessed the intellectual functioning and mental health of the complete Norwegian population with KATP channel neonatal diabetes. Eight sulfonylurea-treated children (five with the p.V59M genotype [KCNJ11]) were assessed using age-matched control subjects with type 1 diabetes. The investigations included a physical and motor developmental examination, cerebral MRI, psychometrical examination, and questionnaires assessing intellectual capabilities and psychiatric morbidity. RESULTS A strong genotype-phenotype correlation was found, revealing the p.V59M genotype as highly associated with substantial intellectual disability, with no significant correlation with the time of sulfonylurea initiation. Consistent with previous studies, other genotypes were associated with minor cognitive impairment. Cerebral MRI verified normal brain anatomy in all but one child. CONCLUSIONS We here presented a comprehensive assessment of intellectual functioning in the largest cohort of p.V59M subjects to date. The level of intellectual disability revealed not only changes the interpretation of other psychological measures but downplays a strong protective effect of sulfonylurea. Within the scope of this study, we could not find evidence supporting an early treatment start to be beneficial, although a weaker effect cannot be ruled out.

中文翻译：

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KATP 通道新生儿糖尿病的智力障碍。

目的 新生儿糖尿病已被证明以基因型-表型依赖性方式与高神经精神疾病发病率相关。然而，不同突变对智力功能的具体影响仍不充分。具体而言，仅对少数发育迟缓的受试者进行了综合评估，造成了对负担最重患者的认识差距。研究设计和方法 我们评估了患有 KATP 通道新生儿糖尿病的完整挪威人群的智力功能和心理健康。使用年龄匹配的 1 型糖尿病对照受试者对八名接受磺脲类药物治疗的儿童（五名具有 p.V59M 基因型 [KCNJ11]）进行了评估。调查包括身体和运动发育检查、脑 MRI、心理测验，以及评估智力和精神病发病率的问卷。结果 发现了强烈的基因型-表型相关性，揭示 p.V59M 基因型与严重的智力障碍高度相关，与磺脲类药物的起始时间没有显着相关性。与之前的研究一致，其他基因型与轻微的认知障碍有关。除一名儿童外，脑部 MRI 证实所有儿童的大脑解剖结构正常。结论 我们在此对迄今为止最大的 p.V59M 受试者队列中的智力功能进行了全面评估。所揭示的智力障碍水平不仅改变了对其他心理措施的解释，而且淡化了磺脲类药物的强大保护作用。在本研究的范围内，