Hyperinsulinism in Developmental Syndromes

Hyperinsulinism is a cause of recurrent and severe hypoglycaemia in the newborn and infancy period. Several developmental genetic syndromes are associated with hyperinsulinism. The underlying molecular mechanisms that lead to hyperinsulinaemic hypoglycaemia in most of these syndromes are unclear. Beckwith-Wiedemann syndrome (BWS) is the most common syndrome associated with hyperinsulinism. The incidence of hyperinsulinism in children with BWS is about 50%. The hyperinsulinaemic hypoglycaemia can be transient, which, in the majority of infants, will be asymptomatic and resolve within the first few days of life. Rarely patients with BWS may require a pancreatectomy. Other overgrowth syndromes such as Soto's syndrome may overlap with BWS and present with hyperinsulinism. Patients with other rare syndromes such as Costello, Timothy and Kabuki syndromes can present with hyperinsulinaemic hypoglycaemia but the genetic mechanism(s) that leads to dysregulated insulin secretion in these syndromes is(are) still unclear. The congenital disorders of glycosylation (CDG) are a rapidly expanding group of metabolic syndromes with a wide symptomatology and severity. They all stem from deficient N-glycosylation of proteins. Hyperinsulinism has been described in congenital disorders of glycosylation, mostly in CDG-Ib but also as the leading symptom in a CDG-Ia patient. In summary, hyperinsulinism may be associated with a large number of developmental syndromes however the underlying molecular mechanisms that cause hyperinsulinism in these syndromes are still unknown. Copyright (C)2009 S. Karger AG, Basel