title: Diagnostic difficulties in glucokinase hyperinsulinism.
abstract: Glucokinase hyperinsulinism is a rare variant of congenital hyperinsulinism caused by activating mutations in the glucokinase gene and has been reported so far to be a result of overactivity of glucokinase within the pancreatic beta-cell. Here we report on a new patient with difficulties to diagnose persistent hyperinsulinism and discuss diagnostic procedures of this as well as the other reported individuals. After neonatal hypoglycemia, the patient was reevaluated at the age of 3 years for developmental delay. Morning glucose after 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). In addition, diagnostic data of the patients reported so far were reviewed. A novel heterozygous missense mutation in exon 10 c.1354G>C (p.Val452Leu) was found and functional studies confirmed the activating mutation. There was no single consistent diagnostic criterion found for our patient and glucokinase hyperinsulinism individuals in general. Often at the time of hypoglycemia low insulin levels were found. Therefore insulin concentrations at hypoglycemia, or during fasting test as well as reactive hypoglycemia after an oral glucose tolerance test were not conclusive for all patients. A glucose lowering effect in extra-pancreatic tissues independent from hyperinsulinism that results in diagnostic difficulties may contribute to underestimation of glucokinase hyperinsulinism. Mutational analysis of the GCK-gene should be performed in all individuals with unclear episodes of hypoglycemia even without documented hyperinsulinism during hypoglycemia. Delay of diagnosis might result in mental handicap of the affected individuals.
authors.affiliation: Department of General Pediatrics, University Children's Hospital, Düsseldorf, Germany. thomas.meissner@med.uni-duesseldorf.de
authors.forename: T
authors.initials: T
authors.lastname: Meissner
authors.forename: J
authors.initials: J
authors.lastname: Marquard
authors.forename: N
authors.initials: N
authors.lastname: Cobo-Vuilleumier
authors.forename: M
authors.initials: M
authors.lastname: Maringa
authors.forename: P
authors.initials: P
authors.lastname: Rodríguez-Bada
authors.forename: M A
authors.initials: MA
authors.lastname: García-Gimeno
authors.forename: E
authors.initials: E
authors.lastname: Baixeras
authors.forename: J
authors.initials: J
authors.lastname: Weber
authors.forename: K
authors.initials: K
authors.lastname: Olek
authors.forename: P
authors.initials: P
authors.lastname: Sanz
authors.forename: E
authors.initials: E
authors.lastname: Mayatepek
authors.forename: A L
authors.initials: AL
authors.lastname: Cuesta-Muñoz
mesh_terms: D002675:Child, Preschool; D005941:Glucokinase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D008297:Male; D020125:Mutation, Missense
chemical_list: D005941:Glucokinase