WOLFRAM (DIDMOAD) SYNDROME

Wolfram syndrome (MIM 222300) is the association of juvenile onset dia betes mellitus and optic atrophy, also known as DIDMOAD (Diabetes Insi pidus, Diabetes Mellitus, Optic Atrophy, and Deafness). Patients prese nt with diabetes mellitus followed by optic atrophy in the first decad e, cranial diabetes insipidus and sensorineural deafness in the sound decade, dilated renal outflow tracts early in the third decade, and mu ltiple neurological abnormalities early in the fourth decade. Other ab normalities include primary gonadal atrophy. Death occurs prematurely, often from respiratory failure associated with brainstem atrophy. Mos t patients eventually develop all complications of this progressive, n eurodegenerative disorder. The pathogenesis is unknown, but the preval ence is 1 in 770 000 in the UK and inheritance is autosomal recessive. A Wolfram gene has recently been mapped to chromosome 4p16.1, but the re is evidence for locus heterogeneity, and it is still possible that a minority of patients may harbour a mitochondrial genome deletion. Th e best available diagnostic criteria are juvenile onset diabetes melli tus and optic atrophy, but there is a wide differential diagnosis whic h includes other causes of neurodegeneration.