PHYH

The PHYH gene provides instructions for making an enzyme called phytanoyl-CoA hydroxylase. This enzyme is critical for the normal function of cell structures called peroxisomes. These sac-like compartments contain enzymes needed to break down many different substances, including fatty acids and certain toxic compounds.

One substance that is broken down in peroxisomes is phytanic acid, a type of fatty acid obtained from the diet (particularly from beef and dairy products). Phytanoyl-CoA hydroxylase is responsible for one of the first steps in breaking down phytanic acid as part of a process known as alpha-oxidation. In subsequent steps, additional enzymes in peroxisomes and other parts of the cell further process this compound into smaller molecules that the body can use for energy.

Researchers suspect that phytanoyl-CoA hydroxylase may have other functions in addition to its role in breaking down phytanic acid. For example, this enzyme appears to help determine the number of peroxisomes within cells and is involved in regulating their activity.

Refsum disease - caused by mutations in the PHYH gene

Mutations in the PHYH gene have been found to cause more than 90 percent of all cases of Refsum disease. About 30 mutations in this gene have been identified. These mutations alter the structure or production of phytanoyl-CoA hydroxylase, which reduces the enzyme's activity. A shortage of this enzyme disrupts the breakdown of phytanic acid in peroxisomes. As a result, phytanic acid and related compounds build up in the body's tissues. The accumulation of phytanic acid is toxic to cells, although it is unclear how an excess of this substance affects vision and smell and causes the other specific features of Refsum disease.