About Wolfram Syndrome
Wolfram Syndrome affects about 1 in 770,000 of the total UK population or 1 in 500,000 children.
What is Wolfram Syndrome?
Wolfram Syndrome is a rare genetic condition leading to late childhood blindness (optic atrophy), diabetes mellitus, diabetes insipidus and deafness, along with other difficulties such as renal and neurological problems. Not all these symptoms are necessarily present in those diagnosed with Wolfram Syndrome, and each one can vary in severity and onset.
Wolfram Syndrome affects about 1 in 770,000 of the total UK population or 1 in 500,000 children, so it is very rare. A consultant paediatrician may only see one affected child in a professional lifetime. There is a lack of local medical knowledge about the condition and how best to manage it. This often results in late diagnosis, a lack of standardised medical care, and can make school life and education difficult for affected children.
- Optic Atrophy essentially means that the optic nerve stops working. Symptoms can often present as difficulty seeing in the classroom at school – or everything going grey. There is currently no treatment for this. Vision problems may be improved with the use of glasses.
- Diabetes Mellitus is the name given when the body cannot convert glucose or sugar to energy because the pancreas is not making enough of the insulin hormone. Symptoms include an enhanced thirst, frequent passing of urine and weight loss. Glucose is passed out in the urine and blood tests show a high level of glucose in the blood. It can be managed by insulin injections/insulin pump, blood glucose monitoring and healthy eating.
- Diabetes Insipidus is the name given when the body cannot concentrate the urine because the posterior pituitary gland in the head is not making enough of the vasopressin hormone. Symptoms again include an enhanced thirst and frequent passing of urine. Urine tests show a very dilute urine. This can be treated by replacing the hormone with a nasal spray or tablets.
- Deafness usually means difficulty in hearing in a crowded room, and difficulty hearing high pitched sounds. Some patients are helped with a hearing aid. In some cases cochlear implants can be a possibility.
- Renal problems include loss of control over bladder function, so patients may wet the bed or have accidents. Some patients are helped by passing a tube or catheter, passed several times a day.
- Neurological problems may occur; these may include loss of balance, sudden jerks of the muscles, depression and breathing problems. Some of these problems may respond to drugs.
A change in the WFS1 gene causes more than 90% of Wolfram Syndrome. This gene provides instructions for producing a protein called Wolframin. The change in the WFS1 gene leads to the production of a Wolframin protein that doesn’t work properly or at all. When the cells do not have enough functioning Wolframin, it causes abnormal cell function.
Diabetes Mellitus occurs in most cases on average at about 5 years of age. The latest onset of diabetes in this condition is about 16 years. Optic atrophy also occurs in most cases at about 10 years of age. The latest onset is about 19 years. If both these features are present by around age 15, Wolfram Syndrome is presumed to exist. Genetic testing can confirm the presence of WS.
Although there is currently no cure for Wolfram Syndrome, each symptom can be improved through treatment. Research groups in the UK and US have identified licensed medicines which may be able to slow or halt the progress of the disease. Both groups are due to begin clinical trials in 2017.
WellChild’s focus is on raising awareness of this condition, and providing support and information to families affected by Wolfram Syndrome.
Research teams in Europe and America are working on the long term goal of finding a cure for Wolfram Syndrome which will reverse the disease process, and on finding a therapy which will restore vision.
In the meantime, their short term goal is to find a way to halt or slow the progression of the condition.
Clinical Trials in 2018
A research team in Birmingham, led by Professor Tim Barrett, have decided to use a medicine in a clinical trial is already used for other conditions, such as epilepsy. This medicine does have several side effects, but may work with Wolfram Syndrome.
Wolfram Syndrome causes vision loss, which the researchers hope the medicine will reduce by 60% or more. The condition also causes loss of brain stem volume, which in turn causes some of the symptoms associated with the condition. The researchers hope that the medicine they have identified will stop or slow the rate of volume loss by 60% or more.
In November 2015 the research team entered an application to the UK Medical Research Council to undertake an efficacy study into the medicine and in October 2016 were awarded £2m for a clinical trial. The team are hoping to recruit around 120 people to take part in the trial, which will include children and adults, and are aiming to start the first trial in early 2018.
Beyond this, the research team in Birmingham are working with bio-tech companies to develop new medicines to stop or reverse the disease progression.
Prof Barrett at 2016 Wolfram Syndrome Conference