Background

The MEHMO (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity) syndrome, which is caused by a hemizygous variant in the EIF2S3 gene on chromosome Xp22, is associated with significant morbidity and mortality. Refractory epileptic seizures and glucose dysregulation are characteristic manifestations of the MEHMO syndrome, which can often diminish patients’ quality of life.

Case

A 5-year-old boy was referred to our hospital because of profound intellectual disability, micropenis, cryptorchidism, central hypothyroidism, and microcephaly. He had neonatal hypoglycemia at birth and later experienced refractory epileptic seizures and developed obesity and insulin-dependent diabetes. A diagnosis of MEHMO syndrome was established on the basis of the patient’s clinical manifestations and de novo novel missense variant in the EIF2S3 gene (NM_001415.3:c.805 T > G) that was detected through whole-exome analysis. Although the patient’s refractory seizures and diabetes had been well controlled with a combination of ketogenic diet (KD) therapy and insulin therapy, acute fatal necrotizing pancreatitis occurred at the age of 68 months. Moreover, despite intensive care, his condition rapidly deteriorated to multiple organ failure and acute respiratory distress syndrome, resulting in death.

Conclusion

The pathophysiology of glucose intolerance in MEHMO syndrome remains to be elucidated; however, recent studies have suggested that EIF2S3 gene variants could lead to glucose dysregulation and β-cell damage in the pancreas. We suspect that in the present case, KD therapy led to an abnormal load on the beta cells that were damaged owing to eIF2γ dysfunction. Therefore, the adverse effects of KD in patients with MEHMO syndrome should be considered.

中文翻译：

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MEHMO综合征难治性癫痫的生酮饮食：急性坏死性胰腺炎的注意事项

背景

MEHMO（智力低下、癫痫发作、性腺机能减退和生殖器功能减退、小头畸形和肥胖症）综合征是由染色体 Xp22 上EIF2S3基因的半合子变异引起的，与显着的发病率和死亡率有关。难治性癫痫发作和葡萄糖失调是 MEHMO 综合征的特征性表现，通常会降低患者的生活质量。

案件

一名 5 岁男孩因严重智力障碍、小阴茎、隐睾、中枢性甲状腺功能减退和小头畸形被转诊至我院。他出生时患有新生儿低血糖症，后来经历了难治性癫痫发作，并发展为肥胖症和胰岛素依赖型糖尿病。MEHMO 综合征的诊断是基于患者的临床表现和EIF2S3 中的从头新错义变异通过全外显子组分析检测到的基因 (NM_001415.3:c.805 T > G)。尽管通过生酮饮食（KD）治疗和胰岛素治疗的结合，患者的难治性癫痫发作和糖尿病得到了很好的控制，但在 68 个月大时发生了急性致命性坏死性胰腺炎。此外，尽管接受了重症监护，但他的病情迅速恶化为多器官衰竭和急性呼吸窘迫综合征，导致死亡。

结论

MEHMO 综合征中葡萄糖耐受不良的病理生理学仍有待阐明；然而，最近的研究表明，EIF2S3基因变异可能导致胰腺中的葡萄糖失调和 β 细胞损伤。我们怀疑在本案例中，KD 疗法导致因 eIF2γ 功能障碍而受损的 β 细胞出现异常负荷。因此，应考虑KD对MEHMO综合征患者的不良反应。