Wolfram syndrome is a condition that affects many of the body's systems. The hallmark features of Wolfram syndrome are high blood sugar (glucose) levels resulting from a shortage of the hormone insulin (a condition called diabetes mellitus) and progressive vision loss due to degeneration of the nerves that carry information from the eyes to the brain (a condition called optic atrophy). People with Wolfram syndrome often also have pituitary gland dysfunction that results in excess urine production (a condition called diabetes insipidus), hearing loss caused by changes in the inner ear (sensorineural deafness), urinary tract problems, reduced amounts of the sex hormone testosterone in males (hypogonadism), or neurological or psychiatric disorders.

Variants (also known as mutations) in the WFS1 gene cause more than 90 percent of Wolfram syndrome type 1 cases. This gene provides instructions for producing a protein called wolframin that is thought to regulate the amount of calcium in cells. A proper calcium balance is important for many different cellular functions, including cell-to-cell communication, the tensing (contraction) of muscles, and protein processing. The wolframin protein is found in many different tissues, such as the pancreas, brain, heart, bones, muscles, lung, liver, and kidneys. Within cells, wolframin is located in the membrane of a cell structure called the endoplasmic reticulum that is involved in protein production, processing, and transport. Wolframin's function is important in the pancreas, where the protein is thought to help process a protein called proinsulin into the mature hormone insulin. This hormone helps control blood glucose levels.

The estimated prevalence of Wolfram syndrome type 1 is 1 in 500,000 people worldwide. Approximately 200 cases have been described in the scientific literature. Only a few families from Jordan have been found to have Wolfram syndrome type 2.

When Wolfram syndrome is caused by variants in the WFS1 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell are altered. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition. Some studies have shown that people who have one copy of a WFS1 gene variant are at increased risk of developing individual features of Wolfram syndrome or related features, such as type 2 diabetes, hearing loss, or psychiatric illness. However, other studies have found no increased risk in such individuals.

Published Date: February 14, 2022
Published By: National Institutes of Health