Genetics and Pathophysiology of Hyperinsulinism in Infancy

Vol. 61, No. 6, 2004

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Review

Genetics and Pathophysiology of Hyperinsulinism in Infancy
Karen E. Cosgrove^a, Ruth M. Shepherd^a, Eva M. Fernandez^a, Anuja Natarajan^b, Keith J. Lindley^c, Albert Aynsley-Green^c, Mark J. Dunne^a

^aSchool of Biological Sciences, Stopford Building, University of Manchester, Manchester,
^bSheffield Children's Hospital, University of Sheffield, Western Bank, Sheffield, and
^cInstitute of Child Health, Great Ormond Street Hospital, London, UK

Address of Corresponding Author

Horm Res 2004;61:270-288 (DOI: 10.1159/000076933)

Key Words

Hyperinsulinism
Hypoglycaemia
ATP-sensitive K⁺ channel
Sulphonylurea receptor
Pancreatic -cell

Abstract

Hyperinsulinism in infancy (HI) is a condition of neonates and early childhood. For many years the pathophysiology of this potentially lethal disorder was unknown. Advances in the genetics, histopathology and molecular physiology of this disease have now provided insights into the causes of beta -cell dysfunction and revealed levels of diversity far in excess of our previous knowledge. These include defects in ion channel subunit genes and mutations in several enzymes associated with beta -cell metabolism and anaplerosis. In most cases, beta -cell pathophysiology leads to an alteration in the function of ATP-sensitive K⁺ channels. This can manifest as 'channelopathies' of K_ATP channels through gene defects in ABCC8 and KCNJ11 (Ch.11p15); or as a result of 'metabolopathies' through defects in the genes encoding glucokinase (GCK, Ch.7p15-p13), glutamate dehydrogenase (GLUD1, Ch.10q23.3) and short-chain L-3-hydroxyacyl-CoA dehydrogenase (HADHSC, Ch.4q22-q26). This review focuses upon the relationship between the causes of HI and therapeutic options.

Author Contacts

Prof. M.J. Dunne
Division of Physiology, Pharmacology and Toxicology, G38
Stopford Building, School of Biological Sciences, The University of Manchester
Oxford Road, Manchester M13 9PT (UK)
Tel. +44 161 275 3921, Fax +44 161 275 5600, E-Mail mark.j.dunne@man.ac.uk

Article Information

Accepted: January 15, 2003
Published online: February 20, 2004
Number of Print Pages : 19
Number of Figures : 5, Number of Tables : 1, Number of References : 169

Medline Abstract (ID 14981344)

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