Refsum disease

of a patient with Refsum disease. Individuals with Refsum disease present with neurologic damage, cerebellar degeneration, and peripheral neuropathy. Most cases are symmetric (affecting the left and right sides of the body equally) and feature both motor and sensory nerve deficits with similar time of onset and rate of disease progression. Approximately 30% of patients with Refsum disease are known to have congenital malformations of bones. The metatarsal and metacarpal bones are the most commonly affected, often being shorter than normal. In theory, this might be the earliest observable symptom of Refsum disease, but such abnormalities are often nonspecific or too minor to be noticed. Rarely, patients with Refsum disease may develop a cardiac arrhythmia. There is evidence that the risk of cardiac problems may increase following an infection or catecholamine-related illness, but this is not firmly established. ==Cause==

Refsum disease is a peroxisomal disorder caused by the impaired alpha-oxidation of branched chain fatty acids resulting in buildup of phytanic acid and its derivatives in the plasma and tissues. This may be due to deficiencies of phytanoyl-CoA hydroxylase or peroxin-7 activity, encoded by the genes PHYH and PEX7, respectively. In at least 90% of cases, Refsum disease is caused by PHYH mutations. PEX7 gene mutations can interrupt the peroxisomal transport of proteins as this gene codes for the peroxin-7 protein receptor. 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 on chromosome 10p13. Refsum disease 2 stems from mutations in the peroxin 7 (PEX7) gene. The PEX7 gene is located in the region of chromosome 6q22-24, and mutations were 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. 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==