PATIENT INFORMATION LEAFLET: WOLFRAM SYNDROME  7th February 2000


What is Wolfram Syndrome?

A syndrome is the name given to a condition where features occur in a consistent pattern, and where the cause is not understood. Wolfram syndrome is named after a Dr Wolfram, who in 1938 described 4 brothers and sisters from the same family with diabetes mellitus and optic atrophy. He worked in the Mayo Clinic in North America, and since then over 200 patients have been described in the world medical literature. It is also called DIDMOAD syndrome, after 4 common features (Diabetes Mellitus, Diabetes Insipidus, Optic Atrophy, and Deafness).

How common is it?

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.

What may happen in the condition?

Diabetes mellitus is the name given when the body cannot convert glucose or sugar to energy, because the pancreas is not making enough insulin hormone. Symptoms include thirst and 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. This usually needs treatment with insulin injections for life.

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 vasopressin hormone. Symptoms again include 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.

Optic atrophy means death of the optic nerve. Symptoms often present as difficulty seeing in the classroom at school, or everything going grey. There is no treatment for this.

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.

How do you tell if you have the condition?

Diabetes mellitus occurs in everyone 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 everyone on average at about 10 years of age. The latest onset is about 19 years. If a young person does not have both these features by about 15 years, he is very unlikely to have Wolfram syndrome.
 
 

What is the outlook for a child with Wolfram syndrome?

The diabetes mellitus can be controlled with insulin injections. The vision problems usually, but not always, get worse, and often a patient will be registered blind within 8 years of diagnosis. About three quarters of patients get diabetes insipidus, and two thirds get deafness, in the teenage years. About two thirds get renal problems in their twenties. About the same proportion get neurological complications in their thirties. However, there may be a subgroup of patients who run a milder course and donít get these additional complications. The oldest patient in the 1995 UK survey was 49 years.

What are the chances of having another affected child?

Wolfram syndrome is inherited as an autosomal recessive condition; this means that both parents carry one abnormal copy of the Wolfram gene, and one normal copy. For a child to be affected, he has to inherit two abnormal copies, one from each parent. The chances of parents having another affected child are about 25%. There is as yet no genetic test during pregnancy to tell if an unborn child is affected.

Will there be a cure for Wolfram syndrome?

Any cure is a long way off. The current research is to understand why mistakes in the Wolfram gene cause the syndrome. There are research groups in America, UK, Germany and Japan all investigating this problem. Wolfram syndrome research in the UK is being supported by Children Nationwide, and SPARKS.

Who can I go to for help?

There is a Wolfram syndrome website where you can register and contact other families affected all over the world (www.wolframsyndrome.org). It is also very important that you show this leaflet to your doctor so that he knows what information you have. If you have any questions about the information in this leaflet, please write to me and I will try and answer.
 

Dr Timothy G Barrett
Senior Lecturer/Consultant Paediatrics
Department of Endocrinology
Birmingham Childrenís Hospital
Steelhouse Lane
Birmingham B4 6NH
UK