A novel homozygous missense mutation in the insulin receptor gene results in an atypical presentation of Rabson-Mendenhall syndrome.

Leprechaunism (Donohue syndrome) and Rabson-Mendenhall syndrome are caused by mutations in the insulin receptor gene and are associated with extreme insulin resistance. Clinically these syndromes appear to represent points on a continuum of severity of receptor dysfunction, rather than completely distinct syndromes. We investigated a Libyan infant with growth retardation, facial dysmorphism (elfin-like features), acanthosis nigricans and hirsutism. Fasting hypoglycaemia and postprandial hyperglycaemia with persistent hyperinsulinemia were found. A novel homozygous missense mutation was found in exon 2, resulting in a substitution of a glycine-132 for a serine in the INSR α-subunit (c.394G > A; p.Gly132Ser). At age ten, he developed diabetes mellitus. At age eleven, patient is still alive with mental retardation and severe growth retardation.