Original Paper

Rapid Genetic Analysis in Congenital Hyperinsulinism
Henrik B.T. Christesen^a, Klaus Brusgaard^b, Jan Alm^e, Sture Sjöblad^f, Khalid Hussain^{g, h}, Claus Fenger^c, Lars Rasmussen^d, Claus Hovendal^d, Timo Otonkoskiⁱ, Bendt Brock Jacobsen^a

Departments of
^aPaediatrics,
^bClinical Genetics,
^cPathology, and
^dSurgical Gastroenterology, Odense University Hospital, Odense, Denmark;
^eDepartment of Paediatrics, Karolinska Institute, Karolinska University Hospital, Stockholm, and
^fDepartment of Paediatrics, University Hospital of Lund, Lund, Sweden;
^gLondon Centre for Paediatric Endocrinology and Metabolism, Great Ormond Street Hospital for Children NHS Trust, and
^hInstitute of Child Health, London, UK;
ⁱHospital for Children and Adolescents and Biomedicum Helsinki, Developmental and Reproductive Biology, University of Helsinki, Helsinki, Finland

Address of Corresponding Author

Horm Res 2007;67:184-188 (DOI: 10.1159/000097063)

  Key Words

• -Cell
• Congenital hyperinsulinism
• Genotype-phenotype correlation
• Hyperinsulinaemic hypoglycaemia

  Abstract

Backgound: In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation. Methods: In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. Results: Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease. One patient had a paternal KCNJ11 mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous ABBC8 mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies. Conclusion: A rapid analysis of the entire ABBC8 and KCNJ11 genes should not stand alone in the preoperative assessment of patients with CHI, except for the case of maternal, or homozygous/compound heterozygous disease-causing mutations.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Henrik B. Thybo Christesen, Consultant, PhD
Department of Paediatrics, Odense University Hospital, Sdr. Blvd. 29
DK-5000 Odense C (Denmark)
Tel. +45 65 41 23 32, Fax +45 65 90 76 07
E-Mail henrik.thybo.christesen@ouh.fyns-amt.dk

  Article Information

Received: Feburary 2, 2006
Accepted: September 21, 2006
Published online: November 15, 2006
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 1, Number of References : 34