Which enzyme is deficient in Refsum disease?
The lack of function of the enzyme (phytanoyl-CoA hydroxylase) leads to a build-up of phytanic acid in blood plasma and tissues. The disorder is inherited in an autosomal recessive manner.
What causes Refsum disease?
Causes. 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.
What part of the brain is affected by Refsum?
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.
What is Refsum?
Definition. Adult Refsum disease (ARD) is a rare genetic disease that causes weakness or numbness of the hands and feet (peripheral neuropathy). Due to a genetic abnormality, people with ARD disease lack the enzyme in peroxisomes that break down phytanic acid, a type of fat found in certain foods.
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 foods contain phytanic acid?
The sources of phytanic acid in the UK diet were confirmed to be foods derived from ruminant animals and fish. They include beef, lamb and products containing the milk fats of cows, sheep and goats. All fish were found to contain phytanic acid roughly in proportion to their fat content.
Is Refsum disease treatable?
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.
How is Refsum disease diagnosed?
Therefore, Refsum disease can be confirmed by a simple blood test that measures the levels of phytanic acid. In addition, most known cases of Refsum disease result from defects in a protein known as phytanoyl-CoA hydroxylase, or PAHX.
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.
Where does alpha-oxidation occur?
Alpha oxidation of fatty acids occurs in the peroxisome as well; this metabolic pathway exists to degrade by-products of chlorophyll, a component of green vegetables in the diet. Phytanic acid is the primary molecule that requires the enzymes dedicated to alpha-oxidation.
Which 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.
Is there a cure for Refsum disease?