Wolfram syndrome
| Wolfram syndrome | |
|---|---|
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| Photographic image of the patient right eye showing optic atrophy without diabetic retinopathy; from Manaviat et al., 2009 | |
| Classification and external resources | |
| Specialty | medical genetics, neurology |
| OMIM | 222300 |
| DiseasesDB | 3787 |
| MeSH | D014929 |
Wolfram syndrome, also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare autosomal-recessive genetic disorder that causes childhood-onset diabetes mellitus, optic atrophy, and deafness as well as various other possible disorders.
It was first described in four siblings in 1938 by Dr. Don J. Wolfram, M.D. The disease affects the central nervous system (especially the brainstem).
Wolfram syndrome was initially thought to be caused by mitochondrial dysfunction due to its symptoms and several reports of mitochondrial mutations. However, it has now been established that Wolfram syndrome is caused by endoplasmic reticulum dysfunction.
Two genetic forms have been described: Wolfram syndrome 1 (WFS1), and Wolfram syndrome 2 (WFS2).
The WFS1 or wolframin gene provides instructions for making the wolframin protein. The WFS1 gene is active in cells throughout the body, with strong activity in the heart, brain, lungs, inner ear, and pancreas. The pancreas provides enzymes that help digest food, and it also produces the hormone insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy.
Within cells, wolframin is located in a structure called the endoplasmic reticulum. Among its many activities, the endoplasmic reticulum folds and modifies newly formed proteins so they have the correct 3-dimensional shape to function properly. The endoplasmic reticulum also helps transport proteins, fats, and other materials to specific sites within the cell or to the cell surface. The function of wolframin is unknown. Based on its location in the endoplasmic reticulum, however, it may play a role in protein folding or cellular transport. In the pancreas, wolframin may help fold a protein precursor of insulin (called proinsulin) into the mature hormone that controls blood glucose levels. Research findings also suggest that wolframin may help maintain the correct cellular level of charged calcium atoms (calcium ions) by controlling how much is stored in the endoplasmic reticulum. In the inner ear, wolframin may help maintain the proper levels of calcium ions or other charged particles that are essential for hearing.
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