Horm Metab Res 2009; 41(4): 320-326
DOI: 10.1055/s-0028-1102922
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Diagnostic Difficulties in Glucokinase Hyperinsulinism

T. Meissner 1 , J. Marquard 1 , N. Cobo-Vuilleumier 2 , M. Maringa 3 , P. Rodríguez-Bada 2 , M. A. García-Gimeno 4 , E. Baixeras 2 , J. Weber 5 , K. Olek 6 , P. Sanz 4 , E. Mayatepek 1 , A. L. Cuesta-Muñoz 2
  • 1Department of General Pediatrics, University Children's Hospital, Düsseldorf, Germany
  • 2Center for the Study of Pancreatic beta-cell Diseases, IMABIS Foundation Carlos Haya Hospital, Malaga, Spain
  • 3Practice, Human Genetics, Bonn, Germany
  • 4Instituto de Biomedicina de Valencia, CSIC and CIBER de Enfermedades Raras (CIBERER), Valencia, Spain
  • 5Integragen, Laboratory, Bonn, Germany
  • 6Parentage Certificate, Laboratory, Gelsenkirchen, Germany
Further Information

Publication History

received 15.08.2008

accepted 14.10.2008

Publication Date:
03 December 2008 (online)


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 β-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 hypogly-cemia. Delay of diagnosis might result in mental handicap of the affected individuals.



T. Meissner

Department of General Pediatrics

University Children's Hospital

Moorenstr. 5

40225 Düsseldorf


Phone: +49/211/811 76 38

Fax: +49/211/811 95 12

Email: [email protected]

A. L. Cuesta-Muñoz, MD, PhD 

IMABIS Foundation and Center

for the Study of Pancreatic

Beta-cell Diseases Carlos

Haya University Hospital

Avda. Carlos Haya no 82

29010 Málaga


Phone: 34/95/129 14 46

Fax: 34/95/261 40 12

Email: [email protected]