Wolfram syndrome: causes, symptoms, diagnosis, treatment

Wolfram syndrome (DIDMOAD syndrome - Diabetes Insipidus, Diabetes Mettitus, Optic Atrophy, Deafness, OMIM 598500) was first described by DJ Wolfram and H.P. WagenerB in 1938 as a combination of juvenile diabetes mellitus and optic atrophy, which was subsequently supplemented by diabetes insipidus and hearing loss. To date, about 200 cases of this disease have been described.

The syndrome is characterized by genetic heterogeneity. It is inherited in an autosomal recessive manner. The gene is localized on chromosome 4p. The pathology is associated with a violation of communication between the nuclear and mitochondrial genomes. In muscles and lymphocytes, 60% of patients have point mutations of mtDNA, which occur in Leber's neurooptic atrophy. Sometimes the syndrome is associated with the presence of a large mitochondrial deletion.

Symptoms of Wolfram syndrome. The disease develops in early childhood (1-8 years). It begins with the appearance of diabetes symptoms. In this case, juvenile (non-autoimmune) diabetes mellitus is formed in combination with atrophy of the optic nerves. Subsequently, diabetes insipidus of central genesis develops (deficiency of vasopressin, observed in 70% of patients) and hearing loss (in 60%), which joins after the age of 10. At first, hearing loss at high frequencies occurs. The disease is progressive.

Half of the patients develop neurological symptoms: myoclonus, seizures, ataxia, dysarthria, nystagmus. Sometimes anosmia, strokes, retinitis pigmentosa, anemia, neutropenia, thrombocytopenia develop.

Renal ultrasound reveals urinary system abnormalities (hydronephrosis, ureteral dilation) in 50%. MRI data reveals brainstem and cerebellar atrophy. EEG and electroretinogram changes are often noted. The RRF phenomenon is often not detected in morphological examination of muscle biopsies. A decrease in glutamate dehydrogenase levels is characteristic. The respiratory chain enzyme activity level is within normal limits.