These mutations in the PEX7 gene generally lead to rhizomelic chondrodysplasia punctata type 1- which impairs development of many parts of the body. Refsum disease is inherited in an autosomal recessive pattern, meaning that it requires both copies of the mutation to inherit the disease. Diagnosis
Histopathologic examination of the skin from a suspected patient commonly shows hyperkeratosis, hyper-granulosis and acanthosis. The presence of cells in the basal and suprabasal layers of the epidermis containing variably sized vacuoles with accumulated lipids is pathognomonic for the disease. Classification
Adult Refsum disease may be divided into the adult Refsum disease 1 and adult Refsum disease 2 subtypes. The former stems from mutations in the phytanoyl-CoA hydroxylase (PAHX aka PHYH) gene, on the PHYH locus at 10p13 on chromosome 6q22-24. It was initially believed this was the sole mutation; however 55% of cases are now attributed to mutations in other genes.Refsum disease 2 stems from mutations in the peroxin 7 (PEX7) gene. This mutation on the PEX7 gene is also on chromosome 6q22-24, and was found in patients presenting with accumulation of phytanic acid with no PHYH mutation.Adult Refsum disease should not be confused with infantile Refsum disease, a peroxisome biogenesis disorder resulting from deficiencies in the catabolism of very long chain fatty acids and branched chain fatty acids (such as phytanic acid) and plasmalogen biosynthesis.
Treatment
Since phytanic acid is not endogenously produced in the human body, individuals with Refsum disease are commonly placed on a phytanic acid-restricted diet and avoid the consumption of fats from ruminant animals and certain fish, such as tuna, cod, and haddock. Grass feeding animals and their milk are also avoided. Recent research has shown that CYP4 isoform enzymes could help reduce the over-accumulation of phytanic acid in vivo. Plasmapheresis is another medical intervention used to treat patients. This involves the filtering of blood to ensure there is no accumulation of phytanic acid. Biological sources of phytanic acid
In ruminant animals, the gut fermentation of consumed plant materials liberates phytol, a constituent of chlorophyll, which is then converted to phytanic acid and stored in fats. Although humans cannot derive significant amounts of phytanic acid from the consumption of chlorophyll present in plant materials, it has been proposed that the great apes (chimpanzees, gorillas and orangutans) as well as other captive non-human primates can derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. See also
Global DARE Foundation (Patient Advocacy Group for Refsum Disease)
The Myelin Project
List of cutaneous conditions

References


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