Makindo Medical Notes

Related Subjects: |Refsum's disease |Abetalipoproteinaemia

About

• Refsum's Disease is a rare autosomal recessive disorder characterized by an inherited defect in the alpha-oxidation of phytanic acid, a type of branched-chain fatty acid found in foods like dairy products, beef, and fish.

Aetiology

• Refsum disease is caused by mutations in genes that encode enzymes necessary for the breakdown of phytanic acid.
• The condition results in the accumulation of phytanic acid and its unsaturated fatty acid derivatives in plasma and tissues, leading to toxic effects on multiple systems.
• Mutations are typically found in the PHYH gene (which encodes phytanoyl-CoA hydroxylase) or the PEX7 gene (which encodes a receptor for proteins required for peroxisomal metabolism).

Types

• Adult Refsum Disease 1: Caused by mutations in the phytanoyl-CoA hydroxylase (PAHX, also known as PHYH) gene.
• Adult Refsum Disease 2: A rarer subtype caused by mutations in the peroxin 7 (PEX7) gene, which affects the transport of enzymes into peroxisomes.

Clinical Features

• Neurological symptoms: Patients often experience progressive cerebellar ataxia, leading to difficulty with coordination and balance.
• Visual symptoms: Retinitis pigmentosa, which leads to progressive vision loss due to damage to the retina, often starting with night blindness.
• Deafness: Progressive sensorineural hearing loss.
• Skin changes: Ichthyosis, or dry, scaly skin, is commonly observed.
• Cardiomyopathy: Some patients develop heart involvement, which can result in arrhythmias or heart failure.
• Peripheral neuropathy: Nerve thickening may lead to muscle weakness and loss of sensation.

Investigations

• Serum Phytanic Acid: Elevated levels of phytanic acid in the blood confirm the diagnosis.
• Cerebrospinal Fluid (CSF): Increased CSF protein levels are found without an increase in white cells (pleocytosis).
• Genetic Testing: Can confirm mutations in the PHYH or PEX7 genes.

Management

• Dietary Management: A phytanic acid-restricted diet is crucial. The goal is to reduce dietary intake of phytanic acid from its usual level (around 50 mg/day) to less than 5 mg/day. This is achieved by avoiding foods high in phytanic acid, such as dairy products, beef, lamb, and certain fish.
• Plasmapheresis: In cases of severe or rapidly worsening symptoms, plasmapheresis can be used to reduce the high plasma phytanic acid level and prevent further accumulation in tissues.
• Topical Treatments: Locally based creams may be used to soften and manage ichthyosis (dry and scaly skin).
• Cochlear Implants: Bilateral cochlear implants may be considered for patients with severe hearing loss.
• Specialist Care: Regular follow-up with ophthalmology (to monitor retinitis pigmentosa) and dermatology (for skin care) is important.

Prognosis

• The prognosis of Refsum’s disease depends on early diagnosis and adherence to a strict phytanic acid-restricted diet. Early dietary intervention and plasmapheresis can significantly improve outcomes and prevent disease progression.