What is Wolfram Syndrome?

Wolfram Syndrome (also called DIDMOAD) is a rare genetic neurodegenerative disease characterized by Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness. It is progressive and life-limiting.

DIDMOAD Acronym:

• Diabetes Insipidus (central)
• Diabetes Mellitus (insulin-dependent)
• Optic Atrophy (progressive vision loss)
• Deafness (sensorineural hearing loss)

Clinical Features (Progressive Onset):

• Diabetes Mellitus (90-100%): Usually first manifestation; onset in childhood (median age 6)
• Optic Atrophy (90-100%): Progressive vision loss; onset childhood/adolescence
• Diabetes Insipidus (70-80%): Central DI; onset adolescence
• Deafness (60-70%): High-frequency hearing loss; gradual
• Neurological: Ataxia, seizures, respiratory failure (brainstem dysfunction)
• Urological: Bladder dysfunction, hydronephrosis
• Psychiatric: Depression, psychosis common

Genetics:

• WFS1 Gene (Most Common): Autosomal recessive
• Affects ER Function: Leads to cell death (pancreas, optic nerve, brain)

Diagnosis:

• Clinical: DM + optic atrophy by age 15 strongly suggests Wolfram
• Genetic Testing: WFS1 mutation
• MRI Brain: Brainstem atrophy

Treatment (Supportive Only - No Cure):

• Diabetes Mellitus: Insulin therapy
• Diabetes Insipidus: Desmopressin (DDAVP)
• Vision: Low vision aids (irreversible)
• Hearing: Hearing aids
• Urological: Treat bladder dysfunction, monitor for hydronephrosis
• Psychiatric Support
• Multidisciplinary Care

Prognosis:

• Progressive neurodegenerative disease
• Median survival: ~30 years (death from brainstem dysfunction, respiratory failure)
• No disease-modifying therapy currently available