Diagnostic difficulties in glucokinase hyperinsulinism

7 páginasGlucokinase Hyperinsulinism (GCK-HI) is a rare variant of congenital hyperinsulinism caused by activating mutations in the glucokinase gene resulting in overactivity of glucokinase within the pancreatic -cell. Until now seven families with this condition have been described. Here we report on a new patient presenting already with increased birthweight and neonatal hypoglycemia. The patient was initially diagnosed to suffer from transient hyperinsulinism and was reevaluated at the age of 3 years with developmental delay. Morning glucose after an overnight fast was 2.5-3.6 mmol/l. Fasting tests revealed supressed insulin secretion at the end of fasting (1.4-14.5 pmol/l). Mutational analysis showed a novel heterozygous missense mutation in exon 10 c.1354G>C (p.Val452Leu). Functional characteristics of GK-V452L clearly illustrated overactivity of this mutation after expression in Escherichia coli as a glutathionyl S-transferase (GST) fusion protein. On the basis of diagnostic difficulties in this patient we reviewed the literature for diagnostic criteria for GCK-HI. There was no single consistent diagnostic criterion found. Insulin concentration at hypoglycemia, fasting test as well as reactive hypoglycemia after an oral glucose tolerance test were not conclusive for all patients. Particularly adults with milder symptoms of hypoglycemia as episodes of extreme hunger or sweatiness were only identified genetically within the family screening. Therefore GCK-HI as an autosomal dominat inherited condition might be underestimated. Mutational analysis of the GCK-gene should be performed in all individuals with unclear episodes of hypoglycemia even without documented hyperinsulinism during hypoglycemia after fasting. Delay of diagnosis might results in mental handicaps of the affected individuals.MEC (P.I3); Dirección General de Investigación Científica y Técnica (SAF2005-08014; SAF2006-12863). Junta de Andalucía (SAS/PI-024/2007). Spanish Novo Nordisk Pharma grant and Instituto de Salud Carlos III (RCMN C03/08 and 02/PI021473) to ALCMPeer reviewe