Refsum disease

The Refsum disease (synonyms: Refsum Kahlke 's disease, Refsum 's disease thiébaut, Heredopathia atactica polyneuritiformis Refsum's disease ) is a Phytansäurespeicherkrankheit. This peroxisomal metabolic disorder is autosomal recessive trait and is named after the discoverer and describer, the Norwegian physician Sigvald Refsum ( 1907-1991 ). It is counted among the hereditary motor neuropathies (type IV).

Cause, symptoms and course

1963 succeeded the now teaching in Hamburg Professor Winfried Kahlke the first biochemical evidence of a hereditary lipid metabolism disorder, as he identified the substrate of Refsum's syndrome, the phytanic acid. Kahlke found by gas chromatography in the exogenous cause of inherited lipid metabolism disorder, an image taken with food breakdown product of chlorophyll, the 3.7.11.15 -tetramethyl- hexadecanoic acid ( phytanic acid ). This discovery inspired the metabolic research worldwide.

The primary biochemical abnormality is the accumulation of phytanic acid, a saturated, branched chain fatty acid which is added only with the food. Since a methyl group is in phytanic acid at the β - position, this fatty acid can not be metabolized directly by mitochondrial or peroxisomal β - oxidation. Accordingly, it is subjected to the α peroxisomal - oxidation of the enzyme Phytanoyl -CoA hydroxylase responsible. If this enzyme is defective, it comes to the clinical appearance of Refsum disease. The disease is genetically heterogeneous The defective enzyme, either the Phytanoyl -CoA hydroxylase itself or Peroxin -7, which is responsible for the transport of the phytanol -CoA hydroxylase in the peroxisomes transport protein.

The main features of the syndrome are retinitis pigmentosa with night blindness and progressive visual field, peripheral polyneuropathy, cerebellar ataxia, and a developing deafness. Other frequent symptoms are nystagmus, ichthyosis, cataracts, loss of sense of smell ( anosmia ) and skeletal deformities in dysplasia of the epiphyses.

First symptom is often night blindness. The course is relapsing with partial remissions and acute exacerbations especially in metabolic stress during surgery, infections, decreased caloric intake, pregnancy or severe diseases in which a lot of phytanic acid from liver and body fat tissue is released. The symptoms starts at an age from early childhood up to 50 years, but mostly in the 2nd or 3rd decade of life. Men and women are affected equally. If left untreated, it leads to deafness and blindness as to the 40.Lebensjahr. Perilous which may occur during acute exacerbations of heart rhythm disorders can be.

Diagnosis

Diagnosis is made by laboratory evidence of phytanic acid in plasma and urine. Even healthy people who are heterozygous carriers, can be recognized.

Treatment

A cure for Refsum 's syndrome is not yet known. The disease can, however, be brought by a consistent phytansäurearme diet largely to a standstill. In this case it is recommended to keep the recorded Phytansäuremenge below 10 mg / day ( the amount of recorded with a normal diet phytanic acid is about 100 mg / day). Foods with a high Phytansäuregehalt are particularly meat of ruminants such as cattle and dairy products. In addition to a vitamin-rich diet phytansäurearmen a sufficient caloric intake is important in order to avoid uncontrolled mobilization of phytanic acid from adipose tissue.

In compliance to the diet peripheral neuropathy may come to a halt and the lesions may heal; in the range of eye and ear, the disease progresses, at least not continue. Includes dietary measures to achieve a satisfactory reduction in the plasma concentration of phytanic acid, possibly plasmapheresis may be required.