ESPE Abstracts (2021) 94 P2-231

Endocrinology Research Centre, Moscow, Russian Federation

Introduction: MEHMO syndrome (mental retardation, epileptic seizures, hypogenitalism, microcephaly, and obesity) is a rare X-linked disorder causes by EIF2S3 gene mutations. This gene encodes a key factor for integrated stress response and initiation of protein synthesis. Since many hormones are proteins or peptides by nature, some of the reported cases of MEHMO syndrome include endocrine disorders: hypopituitarism (hypogonadism, growth hormone deficiency, hypothyroidism, adrenal insufficiency), diabetes mellitus, and transient hypoglycemia. However, the mechanism of hypoglycaemia in the literature is not indicated. Here, we present a boy with MEHMO syndrome and hyperinsulinaemic hypoglycaemia.

Case report: The patient is a second child of non-consanguineous Caucasian family with normal birth weight and length. His 10-year-old brother is healthy. Two male relatives in the mother’s family died at young age: at 5 years (cardiac failure, short stature, microcephaly) and at 8 months (pneumonia). At birth, the proband presented with breathing difficulties but otherwise appeared healthy. At the age of 6 months, he developed first seizures, had a decline in psychomotor development, and was noted to have microcephaly. The boy was diagnosed with epilepsy and started on anticonvulsants with mild success. At the age of 21 months, hyperinsulinaemic hypoglycaemia was detected (glucose 2.2 mmol/l, insulin 28 μIU/ml). The patient was started on diazoxide 5 mg/kg/day with a good response. We assumed the child had a congenital disorder of glycosylation based upon hyperinsulinaemic hypoglycaemia, severe developmental delay, and dysmorphic features (microcephaly, amphora-like face, sloping forehead, high-arched palate, dental diastasis, conical teeth, inverted nipples, and puffy hands and feet). Transferrin isoelectric focusing and genetic tests did not confirm it. At the age of 3 years, whole genome sequencing revealed с.671Т>G mutation in EIF2S3 gene. Like other patients with MEHMO syndrome, our patient has microcephaly, mental retardation, epileptic seizures, overweight, and dysmorphic features. At the age of 5 years, diazoxide was weaned off. There were no signs of diabetes mellitus or hypopituitarism (cortisol, ACTH, IGF-1, free T4, and TSH levels are within normal range). He was also found to have hyperammonemia and started on a low protein diet that lead to a better seizure management.

Conclusion: To the best of our knowledge, this is the first report of hyperinsulinaemic hypoglycaemia in a patient with MEHMO syndrome. Since EIF2S3 mutations alter protein production, overproduction of insulin is counterintuitive. Presumably, the mechanism is similar to MODY1 and MODY3, as in these conditions hyperinsulinaemic hypoglycaemia can anticipate diabetes.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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