Refsum disease, also known as phytanic acid storage disease, is a rare inherited disorder that belongs to a group of conditions called leukodystrophies. It is characterized by the accumulation of phytanic acid in various tissues and organs, leading to neurological and other symptoms. Refsum disease is an autosomal recessive disorder, meaning that individuals inherit two mutated copies of a particular gene (PHYH gene) associated with the condition, one from each parent. The prevalence of Refsum disease is 1 case per 1,000,000 individuals.
Refsum disease genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Critical features of Refsum disease include:
- Phytanic Acid Accumulation: Refsum disease is primarily caused by mutations in the PHYH gene, which encodes the enzyme phytanoyl-CoA hydroxylase. This enzyme is involved in the breakdown of phytanic acid, a fatty acid derived from the diet. In individuals with Refsum disease, the enzyme deficiency leads to the accumulation of phytanic acid in the body.
- Neurological Symptoms: The buildup of phytanic acid affects the nervous system, leading to neurological symptoms. These may include progressive vision loss (due to retinitis pigmentosa), peripheral neuropathy (nerve damage in the extremities), ataxia (difficulty with coordination and balance), and muscle weakness.
- Hearing Loss: Some individuals with Refsum disease may experience hearing impairment.
- Cardiac Involvement: In some cases, cardiac involvement may occur, including arrhythmias or other heart-related issues.
- Ichthyosis: Refsum disease is associated with a skin condition called ichthyosis, which causes dry, scaly skin.
- Dietary Management: Dietary management is an essential aspect of treatment. Since phytanic acid is derived from certain foods, a diet low in phytanic acid is often recommended. This may involve avoiding foods rich in phytanic acid, such as dairy products, red meat, and certain fish.
- Plasmapheresis: In some cases, plasmapheresis, a procedure that removes blood plasma and replaces it with a substitute, may reduce phytanic acid levels.
While there is no cure for Refsum disease, management strategies aim to alleviate symptoms, slow disease progression, and improve the quality of life for affected individuals. Regular monitoring and medical care are essential for addressing the specific needs of individuals with Refsum disease. Genetic counseling is also crucial for affected families to understand the inheritance pattern and the risk of passing the condition to future generations.
The clinical features of Refsum's disease, such as cardiac dysfunction and those of the olfactory and auditory nerves, suggest that excessive phytanic acid concentration could produce cytotoxicity in tissues, especially those with high energy generation (in the form of ATP from fatty acid oxidation), such as the brain and heart.
The accumulation of phytanic acid in Refsum patients is due to mutations in two genes. The gene affected in more than 90% of Refsum cases is PHYH, which encodes the enzyme phytanoyl-CoA hydroxylase. However, in some cases, it is the gene PEX7 that produces the PTS2 ("peroxisomal targeting signal 2 receptor"), a protein involved in the transport of enzymes into the peroxisome.
Refsum disease genetic testing analyzes the 5 most frequent pathogenic mutations of the PHYH gene.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
