Refsum disease
Related Subjects:
|Refsum's disease
|Abetalipoproteinaemia
🧬 Refsum's Disease is a rare autosomal recessive peroxisomal disorder due to defective alpha-oxidation of phytanic acid (a branched-chain fatty acid found in dairy, beef, and certain fish).
Accumulation of phytanic acid in plasma and tissues leads to multisystem toxicity.
📌 Aetiology
- Caused by mutations in genes encoding enzymes for phytanic acid breakdown.
- Most cases due to mutations in PHYH (phytanoyl-CoA hydroxylase); rarer cases due to PEX7 (peroxisomal targeting receptor).
- Failure of phytanic acid metabolism → toxic deposition in nervous system, skin, retina, and heart.
🧬 Types
- Adult Refsum Disease 1: Mutations in PHYH (phytanoyl-CoA hydroxylase).
- Adult Refsum Disease 2: Mutations in PEX7, impairing enzyme transport into peroxisomes.
🩺 Clinical Features
- Neurological: Progressive cerebellar ataxia, peripheral neuropathy, muscle weakness.
- Ophthalmic: Retinitis pigmentosa → night blindness and progressive vision loss.
- ENT: Sensorineural deafness, sometimes requiring cochlear implants.
- Skin: Ichthyosis (dry, scaly skin).
- Cardiac: Cardiomyopathy and arrhythmias in some patients.
- Other: Nerve thickening, gait disturbance, and sensory loss.
🔬 Investigations
- Serum Phytanic Acid: Elevated → diagnostic hallmark.
- CSF: ↑ protein, normal cell count (no pleocytosis).
- Genetic Testing: Confirms PHYH or PEX7 mutations.
💊 Management
- Dietary Restriction: Strict phytanic acid-restricted diet (reduce intake from ~50 mg/day → <5 mg/day). Avoid dairy, beef, lamb, and certain fish.
- Plasmapheresis: For severe cases to rapidly lower phytanic acid levels.
- Topical Therapy: Emollients/keratolytics for ichthyosis.
- Cochlear Implants: For severe hearing loss.
- Specialist Follow-up: Ophthalmology (retinitis pigmentosa monitoring), dermatology (skin), cardiology (cardiac surveillance).
📉 Prognosis
- Good outcome with early diagnosis + strict diet to prevent progression.
- Neurological, cardiac, and retinal damage may be irreversible if advanced at diagnosis.
