Wolfram syndrome Frequently Asked Questions
Q: What are some facts of Wolfram syndrome?
A: Wolfram Syndrome (WS) affects about 1 in 770,000 of the total UK population. The syndrome was first described in 1938 by Dr Wolfram. In 1998, the genetic defect was found simultaneously by two groups, on the short arm of the chromosome 4 (4p). Further studies revealed that this region hosts the gene for WFS1 or Wolframin, a cellular protein located in the endoplasmic reticulum (ER), an organelle inside the cell. The specific functions of the WS protein remain largely unknown. Following the cloning of the WS gene the protein was found to reside in the endoplasmic reticulum (ER) of the cell, and animal models with deficiency were created that were found to have an abnormality of the ER called ER stress which leads to cell death in pancreas and specific areas of the brain causing diabetes mellitus and optic nerve atrophy among others. Mutations in other genes with different location (different chromosome or even in mitochondria) that can give a similar clinical picture has been described. Also, there are several WS patients in whom no genetic mutation have been found. WS is an autosomal recessive disease. Autosomal recessive is a mode of inheritance of genetic traits located on the non-sex determining DNA. A recessive trait only becomes evident when two mutated alleles of the gene are present, meaning that one allele was acquired from the father, another one from the mother, each parent is a carrier for this mutation. New mutations may explain the absence of carrier status in one of the parents.
Q: What is Wolfram syndrome?
A: Wolfram Syndrome (WS) is a rare genetic disease with various disorders. Wolfram Syndrome’s acronym describes these disorders well: DIDMOAD, Diabetes Insipidus, Diabetes Mellitus, Optic Nerve Atrophy and Deafness. Not all of them appear in all patients. Both, diabetes mellitus and optic nerve atrophy are the most consistent clinical findings and are present in nearly all patients. There are less common clinical features associated with this syndrome that have yet to be significantly established. The diagnosis of Wolfram syndrome is clinical based on insulin requiring diabetes and bilateral optic nerve atrophy. Genetic tests are confirmatory in the majority of patients with these clinical symptoms. In a number of patients with Wolfram Syndrome there is no identifiable mutation.
Q: What is the definition for DIABETES MELLITUS?
A: A metabolic disease characterized by abnormally high levels of glucose in the blood, caused by an inherited inability to produce insulin (Type 1) or an acquired resistance to insulin (Type 2). Type 1 diabetes, which typically appears in childhood or adolescence, is marked by excessive thirst, frequent urination, and weight loss and requires treatment with insulin injections. Type 2 diabetes appears during adulthood, usually in overweight or elderly individuals, and is treated with oral medication or insulin. People with either type of diabetes benefit from dietary restriction of sugars and other carbohydrates. Uncontrolled blood glucose levels increase the risk for long-term medical complications including peripheral nerve disease, retinal damage, kidney disease, and progressive atherosclerosis caused by damage to endothelial cells in blood vessels, leading to coronary artery disease and peripheral vascular disease.