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 is the Phyh gene?
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.
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 is Phytanoyl CoA hydroxylase?
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.
What breaks down phytanic acid?
Degradation of phytanic acid takes place by alpha-oxidation inside the peroxisome. A deficiency of its breakdown, leading to elevated levels, can result from either a general peroxisomal dysfunction or from a defect in one of the enzymes involved in alpha-oxidation.
What is Refsum disease?
Refsum Disease – StatPearls – NCBI Bookshelf Refsum disease is one of the four major peroxisomal biogenesis disorders.
What is the prognosis of Refsum’s disease?
Although rare, Refsum’s disease is partially treatable, and early recognition may prevent visual and auditory deterioration. The diagnosis should be considered in any patient with retinitis pigmentosa and an appropriate family history.
Which enzymes are deficient in Refsum’s disease?
The single enzyme deficient in classical Refsum’s disease is phytanoyl‐CoA hydroxylase.
What is the role of phytanic acid in the pathophysiology of Refsum disease?
Levy has suggested that high phytanic acid levels interfere with vitamin A esterification in the retinal pigment epithelium leading to the production of a toxic substance and progressive visual failure. 6 The physiological role of phytanic acid is unknown. Figure 1. The biochemistry of Refsum’s disease. Figure 1.