High Phytanic Acid (VLCFA) Refsum disease.

By SWA

Elevated serum levels of phytanic acid and VLCFAs are the biochemical hallmarks of two distinct inherited neurodegenerative diseases.

Accumulation of phytanic acid is typically due to Refsum disease, a rare neurological disorder resulting from an inherited genetic mutation in the PHYH or PEX7 gene. Symptoms of phytanic acid accumulation encompass peripheral polyneuropathy, cerebellar ataxia, retinitis pigmentosa, anosmia, and hearing impairment.

Abstract: Refsum's Disease, also known as phytanic acid storage disease, arises from inherited defects in the metabolic pathway for phytanic acid, a branched-chain fatty acid derived from the diet. Due to poor metabolism, phytanic acid accumulates in fatty tissues such as the myelin sheaths and organs like the liver and kidneys.

Among other symptoms are the loss of the sense of smell (anosmia), rough and scaly skin (ichthyosis), and, over time, deafness. Elevated plasma phytanic acid levels have also been noted in other conditions.

How is phytanic acid metabolized? Phytanic acid is degraded by alpha-oxidation within the peroxisome. A lack of its efficient metabolism, leading to increased levels, can be attributed to either a broad peroxisomal dysfunction or a specific defect in one of the enzymes that participate in alpha-oxidation.

What is the recommended treatment for Refsum disease?
Treatment for Refsum disease primarily involves reducing the intake of foods rich in phytanic acid. Which foods are sources of phytanic acid? Main sources of phytanic acid include fish, lamb, beef, and dairy products. For therapeutic reasons, it's advised to limit dietary intake to between 10–20 mg/day to reduce serum concentrations.

Which enzyme facilitates the breakdown of phytanic acid? Phytanoyl-CoA hydroxylase is pivotal in the initial stages of phytanic acid degradation as part of alpha-oxidation. Subsequent stages involve other enzymes in peroxisomes and different cellular regions, which further metabolize this compound into smaller molecules, aiding in energy production.

How does Zellweger syndrome relate to Refsum disease? Previously, the severe form was labeled Zellweger syndrome, the intermediate form as neonatal adrenoleukodystrophy (NALD), and the mild form as infantile Refsum disease. These disorders were collectively reclassified under a single diagnostic umbrella when discovered to be variations of the same spectrum of conditions.

More reading: 

X-linked adrenoleukodystrophy: Very long-chain fatty acid metabolism, ABC half-transporters and the complicated route to treatment

 

 

 

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