ESPE Abstracts

Introduction: Monogenic obesity is a heterogeneous group of rare conditions involving less than 5% of the children with obesity. The most common subtypes of monogenic obesity are mutations of the genes MC4R, SIM1, and PCSK1. Rare monogenic obesity forms include also MEHMO syndrome. MEHMO is an X-linked condition characterized by Mental retardation, Epilepsy, Hypogonadism/hypogenitalism, Microcephaly, and Obesity. In our studies we have described the genetics, and endocrine phenotypes of 2 boys with MEHMO syndrome.

Results: Both boys were carrying a frame-shift mutation (I465fs) in the EIF2S3gene inherited from their healthy mothers. EIF2S3 encodes the γ subunit of the eukaryotic translation initiation factor 2 (eIF2), which is involved in protein synthesis. Both probands had microcephaly, hypogonadism, sever psychomotor retardation and seizures. After a short period of failure to thrive, both of them had rapid weight-gain and developed obesity. Neonatal hypoglycemia switched to insulin-dependent non-autoimmune diabetes during the first year of life accompanied by development of panhypopituitarism. These conditions were due to dysregulation and gradual decline of peptide hormone secretion. However, only proteins secreted on demand were affected, as concentration of albumin and IgG immunoglobulins were in normal range. On the other hand one proband had frequent respiratory infections responding well to therapy with immunoglobulins. One of the boys died at the age of 4 years, the second is still alive currently age 11 years.

Conclusions: X-linked MEHMO syndrome is a severe condition caused by a mutation in EIF2S3 encoding the γ subunit of the eukaryotic translation initiation factor 2. The clinical picture results from the damaged protein synthesis. Particularly dysregulation and gradual decline of concentrations of peptide hormones secreted on demand are responsible for the complex endocrine phenotype. Such conditions as MEHMO syndrome help us to understand regulation mechanisms of the endocrine system in children.