Refsum's disease

Refsum's disease (Refsum-Thiébaut disease, Refsum-Thiébaut-Klenk-Kahlke disease), named after Norwegian neurologist Sigvald Bernhard Refsum (1907-1991), is neurological disease that results in the malformation of myelin sheaths around nerve cells. It is a peroxisomal disorder.

Causes

Refsum's disease is caused by faulty enzymes during the alpha-oxidation of phytanic acid resulting in buildup of phytanic acid and its unsaturated fatty acid derivatives in the plasma and tissues.

This in turn can be due to deficiencies of phytanoyl-CoA hydroxylase (chromosome 10) or peroxin-7 (chromosome 6).

Presentation

Patients with Refsum's Disease present with neurologic damage, cerebellar degeneration, and peripheral neuropathy. Onset is most commonly in childhood/adolescence with a progressive course, although periods of stagnation/remission occur. Symptoms also include night blindness, ataxia, scaly skin (ichthyosis), difficulty hearing, and eye problems including cataracts.

Treatment

The most effective therapy in the classic Refsum disease is dietary treatment with a phytanic acid-restricted diet, such as exclusively avoiding consumption of beef, lamb, fatty fish such as tuna, cod, and haddock. Recent research has shown that CYP4 isoform enzymes could eliminate the phytanic acid storage in vivo and patients could try alternative natural remedies with either eatable marine invertebrates or with clofibrate supplement of which the component is usually rich in the excretion of high plant. Currently, there is no clinical data to approve using this xenonbiotic drug for the treatment, perhaps due to its serious adverse effect and the major medical treatment of the disease only relies on the plasmapheresis.

Reaction

Phytol (from chlorophyll in plant foods) ---> phytanic acid -x-> pristanic acid ---> propionyl CoA due to the composition of starch and the chemical and molecular breakdown of fatty acids refsum's disease can be treated by creating glucose in an excess amount