A research team led by Michael MacDonald, MD, has discovered a genetic cause of a Type I diabetes syndrome that has puzzled investigators for 85 years.
In the July issue of the journal Diabetes, the team describes its discovery of a gene mutation that, when combined with hyperglycemia from poorly controlled diabetes in children, causes Mauriac Syndrome, a rare disease that presents as massive liver enlargement, growth failure and delayed puberty.
Specifically, the team sequenced the DNA of a patient with the syndrome, looking at the genes that encode all of the glycogen metabolism enzymes. They found a mutated gene, inserted it into human liver cells in cell culture and found that the mutated gene caused high levels of glycogen accumulation in the human liver cells, thus causing the liver enlargement.
The patient's mother had the same gene mutation, but did not have diabetes or an enlarged liver. The patient's father did not have the gene mutation or an enlarged liver, but did have poorly controlled Type I diabetes. The case demonstrates how the interaction between the gene mutation and hyperglycemia is the root cause of Mauriac Syndrome.
Read the full study here.