Makindo Medical Notes

About

• 🧬 Wolfram syndrome (DIDMOAD) is a rare neurodegenerative disorder.
• 💡 Acronym: DIDMOAD = Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness.

Aetiology

• 🧪 Caused by defects in the WFS1 gene (chromosome 4), leading to mitochondrial dysfunction and endoplasmic reticulum stress.
• 🔗 Less commonly linked to other nuclear or mitochondrial DNA mutations.

Features

• 💧 Diabetes Insipidus – impaired vasopressin secretion → polyuria & polydipsia.
• 🍬 Diabetes Mellitus – usually non-autoimmune, insulin-dependent onset in childhood.
• 👁️ Optic atrophy – progressive loss of vision due to optic nerve degeneration.
• 🎧 Sensorineural deafness – often progressive, bilateral hearing loss.

Clinical Presentation

• 🧑‍🦱 Usually presents in childhood or adolescence.
• 💦 Polyuria and polydipsia from DI.
• 👓 Progressive visual loss (optic atrophy).
• 🔊 Hearing impairment due to SNHL.
• ⚠️ Other: ataxia, neuropathy, and psychiatric illness can develop in later stages.

Investigations

• 🩸 U&E: Hypernatraemia from uncontrolled DI.
• 🍭 Glucose: High plasma glucose confirms DM.
• 💉 Water deprivation test: Confirms central DI.
• 🧬 Genetic testing: WFS1 mutation analysis (definitive diagnosis).

Management

• 💊 Symptomatic and supportive: manage DM with insulin, DI with desmopressin.
• 👁️ Ophthalmology: low-vision aids, regular monitoring of optic atrophy.
• 🎧 Audiology: hearing support (hearing aids/cochlear implant if needed).
• 🤝 Multidisciplinary care essential – endocrinology, neurology, ophthalmology, ENT, psychology.

📚 Exam tip: Remember DIDMOAD as the classic tetrad. The key distinction is that DM in Wolfram syndrome is non-autoimmune (unlike type 1 DM). Always think of Wolfram syndrome in a young patient with DM plus progressive vision and hearing loss. 🚨