An investigation into heterozygosity for glycogen storage disease as a possible cause of glycogenic hepatopathy in type 1 diabetes

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Glycogenic hepatopathy is an uncommon condition causing painful liver enlargement, impaired liver function and in the long term, may cause irreversible liver fibrosis in young individuals with type 1 diabetes. We wish to study whether there may be an underlying genetic cause which increases the risk for people to develop this condition. Glycogenic hepatopathy is thought to occur when there are concomitant high blood glucose levels and elevated insulin levels, and may be associated with elevated serum lactate levels. This triad contributes to increased liver glycogen storage ultimately culminating in liver damage. Excess hepatic glycogen storage is also characterstic of glycogen storage diseases, which are a group of heritable conditions where storage of glucose or release of glucose from storage does not occur normally, and can cause enlargement of the liver similar to glycogenic hepatopathy. People who have glycogen storage diseases typically have a mutation (change) in both copies of the causative gene. However, we are addressing the question of whether having type 1 diabetes with only one copy of the mutation for glycogen storage diseases (heterozygosity) is sufficient to precipitate abnormal glucose storage or release, resulting in the development of glycogenic hepatopathy. In support of our hypothesis, strict blood glucose control reverses glycogenic hepatopathy. This pilot study will help clarify whether genetic sequencing for mutations which cause glycogen storage disorders can identify young people with type 1 diabetes at risk of glycogenic hepatopathy. This will enable us to alter clinical practice by facilitating genetic counselling of these patients on the particular importance of tight blood glucose control in their case and make diagnosis of this disorder less invasive. Indeed, currently, a definitive diagnosis of glycogenic hepatopathy can only be made by liver biopsy. This may be hazardous particularly in young children, a common time when the disorder first presents. Determining whether there is a genetic mutation associated with glycogenic hepatopathy may enable diagnosis to be made without having to perform a liver biopsy.

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