Refsum's disease
Encyclopedia
Refsum disease, also known as classic or adult Refsum disease, heredopathia atactica polyneuritiformis, phytanic acid
oxidase deficiency and phytanic acid
storage disease, is an autosomal
recessive neurological disease that results from the over-accumulation of phytanic acid in cells and tissues. It is one of several disorders named after Norwegian neurologist Sigvald Bernhard Refsum (1907–1991).
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.
, scaly skin (ichthyosis
), difficulty hearing, and eye problems including cataracts.
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. In general, Refsum disease is caused by PHYH mutations.
. Plasmapheresis
is another medical intervention used to treat patients.
, 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 (bonobos, chimpanzees, gorillas, and orangutans) can derive significant amounts of phytanic acid
from the hindgut fermentation
of plant materials.
Phytanic acid
Phytanic acid is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish. Western diets are estimated to provide 50-100 mg of phytanic acid per day...
oxidase deficiency and phytanic acid
Phytanic acid
Phytanic acid is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish. Western diets are estimated to provide 50-100 mg of phytanic acid per day...
storage disease, is an autosomal
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
recessive neurological disease that results from the over-accumulation of phytanic acid in cells and tissues. It is one of several disorders named after Norwegian neurologist Sigvald Bernhard Refsum (1907–1991).
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, while the latter stems from mutations in the peroxin 7 (PEX7) gene.Adult Refsum disease should not be confused with infantile Refsum disease
Infantile Refsum disease
Infantile Refsum disease , also called infantile phytanic acid storage disease, is a rare autosomal recessive congenital peroxisomal biogenesis disorder within the Zellweger spectrum. These are disorders of the peroxisomes that are clinically similar to Zellweger syndrome and associated with...
, 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
Phytanic acid
Phytanic acid is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish. Western diets are estimated to provide 50-100 mg of phytanic acid per day...
) and plasmalogen
Plasmalogen
Plasmalogens are a type of ether phospholipid characterized by the presence of a vinyl ether linkage at the sn-1 position and an ester linkage at the sn-2 position . In mammals, the sn-1 position is typically derived from C16:0, C18:0, or C18:1 fatty alcohols while the sn-2 position is most...
biosynthesis.
Characteristics
Individuals with Refsum disease present with neurologic damage, cerebellar degeneration, and peripheral neuropathy. Onset is most commonly in childhood/adolescence with a progressive course, although periods of stagnation/remission occur. Symptoms also include night blindness, ataxiaAtaxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, scaly skin (ichthyosis
Ichthyosis
Ichthyosis is a heterogeneous family of at least 28, generalized, mostly genetic skin disorders. All types of ichthyosis have dry, thickened, scaly or flaky skin...
), difficulty hearing, and eye problems including cataracts.
Cause
Refsum disease is a peroxisomal disorderPeroxisomal disorder
Peroxisomal disorders represent a class of medical conditions caused by defects in peroxisome functions. This may be due to defects in single enzymes important for peroxisome function or in peroxins, proteins encoded by PEX genes that are critical for normal peroxisome assembly and...
caused by the impaired alpha-oxidation of branched chain fatty acids resulting in buildup of phytanic acid
Phytanic acid
Phytanic acid is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish. Western diets are estimated to provide 50-100 mg of phytanic acid per day...
and its derivatives in the plasma and tissues. This may be due to deficiencies of phytanoyl-CoA hydroxylase or peroxin-7
Peroxin-7
Peroxin-7 is a receptor associated with Refsum's disease and rhizomelic chondrodysplasia punctata type 1.-External links:* *...
activity. In general, Refsum disease is caused by PHYH mutations.
Treatment
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. Recent research has shown that CYP4 isoform enzymes could help reduce the over-accumulation of phytanic acid in vivoIn vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
. Plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
is another medical intervention used to treat patients.
Biological sources of phytanic acid
In ruminant animals, the gut fermentation of consumed plant materials liberates phytolPhytol
Phytol is an acyclic diterpene alcohol that can be used as a precursor for the manufacture of synthetic forms of vitamin E and vitamin K1. In ruminants, the gut fermentation of ingested plant materials liberates phytol, a constituent of chlorophyll, which is then converted to phytanic acid and...
, a constituent of chlorophyll
Chlorophyll
Chlorophyll is a green pigment found in almost all plants, algae, and cyanobacteria. Its name is derived from the Greek words χλωρος, chloros and φύλλον, phyllon . Chlorophyll is an extremely important biomolecule, critical in photosynthesis, which allows plants to obtain energy from light...
, which is then converted to phytanic acid
Phytanic acid
Phytanic acid is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish. Western diets are estimated to provide 50-100 mg of phytanic acid per day...
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 (bonobos, chimpanzees, gorillas, and orangutans) can derive significant amounts of phytanic acid
Phytanic acid
Phytanic acid is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish. Western diets are estimated to provide 50-100 mg of phytanic acid per day...
from the hindgut fermentation
Hindgut fermentation
Hindgut fermentation is a digestive process seen in monogastric herbivores, animals with a simple, single-chambered stomach. Cellulose is digested with the aid of symbiotic bacteria. The microbial fermentation occurs in the digestive organs that follow the small intestine, namely the large...
of plant materials.