Wolfram syndrome

At least one mutation in the CISD2 gene has been found to cause Wolfram syndrome. This condition is characterized by a lack of insulin leading to increased blood glucose (diabetes mellitus), a degeneration of nerves that carry information from the eyes to the brain (optic atrophy), and a number of other features involving the urinary tract, the brain, and hearing. People with this CISD2 gene mutation also experience gastrointestinal ulcers and excessive bleeding after injury.

The CISD2 gene mutation that causes Wolfram syndrome replaces the amino acid glutamic acid with the amino acid glutamine at position 37 in the CISD2 protein (written as Glu37Gln or E37Q). This mutation results in an abnormally small, nonfunctional CISD2 protein. As a result, the function of the mitochondria is impaired and they eventually break down. Since the mitochondria provide energy to cells, the loss of mitochondria leads to decreased energy for cells. Cells that do not have enough energy to function will eventually die. Cells with high energy demands, such as nerve cells in the brain, eyes, or gastrointestinal tract, are most susceptible to cell death due to reduced energy. The gradual loss of cells in various body systems likely causes the signs and symptoms of Wolfram syndrome. When Wolfram syndrome is caused by CISD2 gene mutations, it is sometimes referred to as Wolfram syndrome type 2.