BACKGROUND Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) is an extremely rare autosomal recessive disorder with variable expressivity, caused by biallelic mutations in the PTRH2 gene. Core features are global developmental delay or isolated speech delay, intellectual disability, sensorineural hearing loss, ataxia, and pancreatic insufficiency (both exocrine and endocrine). Additional features may include postnatal microcephaly, peripheral neuropathy, facial dysmorphism, and cerebellar atrophy. In literature, there are only a few anecdotal case reports and none of the previous cases presented with diabetic ketoacidosis. METHODS We are reporting a 12-year old adolescent girl with mild intellectual disability who presented with fever, pain abdomen for 2 days, and fast breathing for one day. RESULTS Her random blood sugar was 472 mg/dl and arterial blood gas revealed high anion gap metabolic acidosis. Urine examination showed ketonuria. On further evaluation, she was found to have demyelinating sensorimotor polyneuropathy and sensorineural hearing loss. Neuroimaging and other ancillary investigations were normal. Whole exome sequencing revealed a novel homozygous single base pair duplication in exon 1 of the PTRH2 gene (c.127dupA, p.Ser43LysfsTer11), confirming the diagnosis of IMNEPD. CONCLUSIONS Apart from describing a novel single base pair duplication causing protein truncation in the PTRH2 gene for the first time, our case also expanded the clinical spectrum of IMNEPD, as this is the first case with seemingly pure neurodevelopmental phenotype, who later developed diabetes mellitus, without any exocrine pancreatic abnormality. IMNEPD should be considered in children or adolescents with global developmental delay or intellectual disability when they develop diabetes mellitus.

中文翻译：

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由 PTRH2 基因中的新型单碱基对重复引起的智力障碍少女的糖尿病：扩大 IMNEPD 的临床范围

背景婴儿型多系统神经系统、内分泌和胰腺疾病 (IMNEPD) 是一种极其罕见的常染色体隐性遗传病，具有可变的表现力，由 PTRH2 基因中的双等位基因突变引起。核心特征是全面发育迟缓或孤立性言语迟缓、智力障碍、感音神经性听力损失、共济失调和胰腺功能不全（外分泌和内分泌）。其他特征可能包括出生后小头畸形、周围神经病变、面部畸形和小脑萎缩。在文献中，只有少数轶事病例报告，以前的病例均未出现糖尿病酮症酸中毒。方法 我们报告了一名患有轻度智力障碍的 12 岁少女，她出现发烧、腹痛 2 天、呼吸急促 1 天。结果 她的随机血糖为 472 mg/dl，动脉血气显示高阴离子间隙代谢性酸中毒。尿液检查显示酮尿。在进一步评估中，她被发现患有脱髓鞘性感觉运动性多发性神经病和感音神经性听力损失。神经影像学和其他辅助检查正常。全外显子组测序显示 PTRH2 基因（c.127dupA，p.Ser43LysfsTer11）的外显子 1 中出现新的纯合单碱基对重复，证实了 IMNEPD 的诊断。结论除了首次描述了导致 PTRH2 基因蛋白质截断的新型单碱基对重复外，我们的病例还扩展了 IMNEPD 的临床谱，因为这是第一个看似纯神经发育表型的病例，后来发展为糖尿病，无胰腺外分泌异常。