Diabetes Over View

Didmoad Syndrome

The ADA (American diabetes association) classifies diabetes as type 1 or insulin dependant, type 2 or non-insulin dependant and diabetes associated with many other syndromes. The third class is a conglomerate of rare syndromes in which diabetes is associated with varying symptoms and wolfram syndrome is one such syndrome.

Wolfram syndrome or the DIDMOAD syndrome is a group of symptoms like Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness. This is a genetic neuro degenerative disease that presents with the following features

Diabetes insipidus

Diabetes insipidus is present in about 70% of all the patients with wolfram syndrome and is due to the deficiency of a hormone called the Arginine vasopressin, from the posterior part of the Pitutory gland. Its presentation is in the second decade of life i.e. from 10 to 19 years of age.

Diabetes mellitus

This is present in all the patients diagnosed with wolfram syndrome and the presentation is that of the juvenile onset diabetes, with its onset in the first decade of life i.e from birth to 9 years of life. It happens due to the deficiency of the hormone Insulin, which controls the glucose metabolism of the body.

Optic atrophy

This again presents early in the first decade of life itself and is present in all the patients of wolfram syndrome. This presents as blindness and is due to the progressive and unrelenting damage to the optic nerve, the nerve of the eye.

Deafness

The condition is reported in only 66% of the patients of Didmoad syndrome and is due to the damage to the nerve of the inner ear.

Other features

Other neurological deficits

In addition to blindness and deafness, there are many other features like difficulty in balancing and walking (ataxia), increased reaction to sudden sounds or movements (startle myoclonus) etc that a patient with wolfram syndrome experiences. These are present in about 60% of the total patients.

Psychiatric

About 25% of the patients have major psychological problems like depression, psychosis, organic brain syndrome etc.

Urological

A person presented with the syndrome will face difficulties in urination etc since the nerves associated with the bladder are also damaged.

Gastro intestinal

There can be alternating constipation or diarrhea.

Pathology

The basis of the entire syndrome is by a progressive neural degeneration of nerves and their neural centers. The basic mechanism of action is as yet not known, but there definitely is a component of demyelination of nerves ,as in Multiple sclerosis.

Genetics

As discussed earlier, this is a hereditary disorder in which the defect is transmitted through the genes of mitochondria, the powerhouse of the cell providing energy to the cell.

Inheritance

Being an autosomal recessive disorder, the chance of a person suffering from it increases when there is a history of similar disease in both the parents. So it is advisable not to go in for consanguinous marriages in case of people with a history in the family.

Prognosis

It is a uniformly fatal disease, with the mean life expectancy of a patient being around 3 decades. The cause of death is due to respiratory failure (as the centers of respiration in the brain stem get damaged), aspiration pneumonia (as the nerves of the throat are damaged), seizures, kidney failure (due to the back pressure of the urine), hypoglycemia (low sugar) or suicides due to the severe psychiatric illnesses etc.

Diagnosis

The first indication of this disease can be suspected whenever a patient of juvenile onset diabetes presents with blindness, particularly in cases of Caucasians where the incidence is more. Once suspected additional tests have to be carried out in order to confirm that diabetes is of type 1 and that the blindness is due to optic atrophy. Once confirmed, then screening tests or other features like Ultra sound of the abdomen for abnormalities of the urinary tract, Base line MRI for cranial diabetes insipidus, Hearing test for sensory neural hearing defects etc have to be performed

Management.

The medical management aims at treating the diabetes mellitus, supplementation of hormone for diabetes insipidus, rehabilitation for the hearing and visual losses etc have to be the main stay of the treatment.

Differential diagnosis

In case of diabetes and deafness in children congenital rubella syndrome, Leber's hereditary optic atrophy and thiamine responsive anemia have all to be considered.

The association of DM and optic atrophy also occurs in Friedrich's ataxia, Refsum disease, Alstrom syndrome, Lawrence- Moon syndrome, Kearn- Sayre syndrome and deafness and diabetes in the 3243 mitochondrial DNA mutation.

All in all this is a disease, which though rare has a uniformly tragic ending and hence requires further research into it.