Intellectual Disability in KATP Channel Neonatal Diabetes
Intellectual Disability in KATP Channel Neonatal Diabetes
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DOI：
10.2337/dc19-1013
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发表时间：
2020-03-01
期刊：
影响因子：
16.2
通讯作者：
Njolstad, Pal R.
中科院分区：
文献类型：
--
作者：
Svalastoga, Pernille;Sulen, Asta;Njolstad, Pal R.
目的：新生儿糖尿病与神经精神疾病的发病率呈基因型-表型依赖关系。然而，不同突变对智力功能的具体影响仍然没有得到充分的表征。具体而言，仅对少数发育迟缓受试者进行了全面评估，造成了对负担最重患者的知识缺口。研究设计和方法：我们评估了整个挪威K-ATP通道新生儿糖尿病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8名磺脲类药物治疗的儿童（5名具有p.V59M基因型[KCNJ 11]）进行评估。调查包括身体和运动发育检查，脑MRI，心理测量学检查，以及评估智力能力和精神病发病率的问卷调查。结果发现一个强的基因型-表型相关性，揭示p.V59M基因型与实质性智力残疾高度相关，与磺酰脲类药物开始使用的时间无显著相关性。与以前的研究一致，其他基因型与轻微的认知障碍有关。脑MRI证实除一名儿童外，所有儿童的脑解剖结构正常。结论：我们在这里提出了一个全面的评估，迄今为止最大的队列p.V59M受试者的智力功能。揭示的智力残疾水平不仅改变了其他心理措施的解释，但低估了磺酰脲类药物的强大保护作用。在这项研究的范围内，我们无法找到支持早期治疗开始有益的证据，尽管不能排除较弱的效果。
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 K-ATP 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.