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Severe hypoglycaemia linked to mutation in insulin signalling gene

10 October 2011
Appeared in BioNews 628

Mutations in a single gene have been identified as the cause of a severe and life-threatening form of hypoglycaemia.

Scientists from the University of Cambridge studied the genetic code of three children with a rare form of hypoglycaemia which affects only 1 in 100,000 people, causing dangerously low blood sugar levels. Their report, published in Science, found a mutation in the AKT2 gene in all three cases.

Normally AKT2 transmits insulin signals to body tissue to regulate sugar levels, but this mutation causes the body to respond as if insulin is always present. This lowers the blood sugar levels unnecessarily.

Dr Robert Semple, Wellcome Trust clinician scientist at the Institute of Metabolic Science, University of Cambridge, said: 'Fear of low blood sugar has dominated the lives of these patients and their families, and for many years the lack of an obvious cause has added to their anxiety'.

To date sufferers of this apparently genetic form of hypoglycaemia have relied upon surgical insertion of a feeding tube into the stomach to deliver food overnight when blood glucose levels would otherwise plummet and cause fits.

Lead researcher Professor Stephen O'Rahilly told the BBC that cancer drugs targeting ATK1 were already available, and that they also act against AKT2, implying that pharmaceutical intervention may soon be possible.

Hypoglycaemia is usually characterised by excessive levels of circulating insulin leading to little sugar remaining in the bloodstream. It commonly affects patients with type 1 diabetes and is accompanied by symptoms of seizures and unconsciousness. In this rarer form there is no detectable insulin in the bloodstream at all and its cause has perplexed scientists until now.

An Activating Mutation of AKT2 and Human Hypoglycemia
Science |  7 October 2011
Scientists identify cause of severe hypoglycemia
Eurekalert |  6 October 2011
Severe hypoglycaemia cause found
BBC |  7 October 2011
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