Which enzyme is deficient in Refsum disease?

Patients with Refsum disease are unable to degrade phytanic acid because of a deficient activity of phytanoyl-CoA hydroxylase (PhyH), a peroxisomal enzyme catalyzing the first step of phytanic acid alpha-oxidation. Refsum disease can be classified as a peroxisome biogenesis disorder.

What causes Refsum disease?

More than 90 percent of all cases of Refsum disease result from mutations in the PHYH gene. The remaining cases are caused by mutations in a gene called PEX7. The signs and symptoms of Refsum disease result from the abnormal buildup of a type of fatty acid called phytanic acid.

Can Refsum disease be cured?

Although there is no cure, phytanate levels in Refsum disease patients can be reduced by plasmapheresis and a strict diet. Pharmacological up-regulation of the omega-oxidation of phytanic acid may form the basis of the new treatment strategy for adult Refsum disease in the near future.

What foods contain phytanic acid?

Fish, lamb, beef, and dairy products are rich sources of phytanic acid. Restriction of dietary consumption to 10–20 mg/day is required to decrease serum levels.

Why does phytanic acid accumulate in Refsum disease?

Phytanic acid storage disease (known also as Refsum’s Disease) is caused by inherited defects in the metabolic pathway for phytanic acid, a dietary branched-chain fatty acid. Poorly metabolized phytanic acid accumulates in fatty tissues, including myelin sheaths, and in organs including the liver and kidneys.

What part of the brain is affected by Refsum disease?

cerebellum). The incoordination and unsteadiness is due to the brain’s failure to regulate the body’s posture, as well as the strength and direction of the body’s movements. This stems from the demylination (or short-circuiting) of the nerve cells in the brain.

Where does phytanic acid come from?

Specifically, PHYH codes for the phytanoyl-CoA hydroxylase enzyme that is used in the peroxisome to break down phytanic acid. Phytanic acid comes from the diet and is derived from bacterial fermentation of green plants or algae.

How common is Refsum disease?

About 60 cases of Refsum disease (RD) have been reported worldwide. Prevalence rates are not known but the disorder may be underdiagnosed. Prevalence has been estimated to be 1/1,000,000 in the United Kingdom. Males and females are affected equally.

Is Refsum disease fatal?

Although it is rare, if phytanic acid levels become very high in people with Refsum disease, then a cardiac arrhythmia (irregular heartbeat) can occur which could be life threatening.

How is Refsum disease treated?

Treatment of Refsum disease requires minimizing intake of beef, lamb, certain seafood, and dairy products while maintaining carbohydrate intake, which helps prevent phytanic acid from entering the blood from fat or liver stores.

Why is phytanic acid important?

Phytanic acid is a branched-chain fatty acid that accumulates in a variety of metabolic disorders. High levels of phytanic acid found in patients can exceed the millimolar range and lead to severe symptoms. Degradation of phytanic acid takes place by alpha-oxidation inside the peroxisome.

Who discovered Refsum?

Refsum disease was first recognized as a distinct disease entity by Sigvald Refsum in the 1940s. The discovery of markedly elevated levels of the branched-chain fatty acid phytanic acid in certain patients marked Refsum disease as a disorder of lipid metabolism.