Refsum's Disease: Nature of the Enzyme Defect

  title={Refsum's Disease: Nature of the Enzyme Defect},
  author={D. Steinberg and J. Herndon and B. Uhlendorf and C. Mize and J. Avigan and G. Milne},
  pages={1740 - 1742}
Two siblings with Refsum's disease, an inherited disorder of lipid metabolism, oxidized intravenously injected uniformly labeled phytanic acid-C14 at rates less than 5 percent of those found in normal subjects. The defect in oxidation of phytanic acid persisted in cultures of fibroblasts from the patients' skin. The rate of oxidation of the phytanic acid-C14 was less than 1 percent of that found in cultures of fibroblasts from normal skin. However, pristanic acid, previously shown to be the… Expand
Refsum's disease: characterization of the enzyme defect in cell culture.
Elevated levels of free phytanate in the medium were no more toxic to HAP cells than to control cells over the 48- to 72-hr exposures involved in these studies, as evidenced by morphologic criteria and by ability to oxidize labeled palmitate. Expand
Patterns of Refsum's disease. Phytanic acid oxidase deficiency.
The data suggest that the clinical diagnosis of Refsum's disease in children is more difficult because the full spectrum of clinical features usually observed in adults with the disorder is not always present and a failure to detect a raised plasma phytanic acid value may not necessarily indicate normal fibroblast phytic acid oxidase activity. Expand
Phytanic acid oxidase deficiency . Patterns of Refsum ' s disease
Four children each exhibiting a profound deficiency of phytanic acid oxidase activity in cultured skin fibroblasts but with very different phenotypes, are described. A consistently raised plasmaExpand
Phytanic acid oxidase activity in cultured skin fibroblasts. Diagnostic usefulness and limitations.
An assay system for the degradation of phytanic acid in cultured skin fibroblasts makes it possible to single out patients with Refsum's disease from the cob-web of clinically related conditions, but the sensitivity is not good enough to diagnose the heterozygous state. Expand
Peroxisomes in fibroblasts from skin of Refsum's disease patients.
In the adult form of Refsum's disease, which is the more thoroughly studied variety, peroxisomes in fibroblasts are not diminished in number, which contrasts with a recent report concerning a case of what is thought to be an infantile form of the disorder. Expand
Diagnosis of Refsum's disease using [1‐14C]phytanic acid as substrate
  • A. Poulos
  • Biology, Medicine
  • Clinical genetics
  • 1981
No obvious relationship was found between the degree of residual activity, the level of plasma phytanate, and the patient's clinical condition and history, but small differences in residual activity were observed in the different cell lines. Expand
Localization of the oxidative defect in phytanic acid degradation in patients with Refsum's disease.
These studies support the conclusion that the defect in phytanic acid oxidation in Refsum's disease is located in the first step of phytic acid degradation, that is, in the alpha oxidation step leading to formation of alpha-hydroxyphytanic acid. Expand
Refsum's disease: a peroxisomal disorder affecting phytanic acid alpha-oxidation.
The biochemistry of the alpha-oxidation pathway may be linked to the regulation of metabolic pathways controlled by isoprenoid lipids, involving calcineurin or the peroxisomal proliferator activating alpha-receptor. Expand
Infantile Refsum's disease: Biochemical findings suggesting multiple peroxisomal dysfunction
Infantile Refsum's disease was diagnosed in three male patients, presenting with facial dysmorphia, retinitis pigmentosa, neurosensory hearing loss, hepatomegaly, osteopenia and delayed growth andExpand
Refsum disease: a defect in the alpha-oxidation of phytanic acid in peroxisomes.
The data described here clearly demonstrate that pathognomonic accumulation of phytanic acid in patients with Refsum disease is due to the deficient activity of peroxisomal alpha-oxidation enzyme system. Expand


Studies on the metabolic error in Refsum's disease.
Patients with Refsum's disease have a relative block in the degradation of phytanic acid and possibly other similar branched-chain compounds, which may relate to a deficiency in mechanisms for release of phydanic acid from stored ester forms or, more probably, to reactions essential to oxidative degradation of the carbon skeleton. Expand
Alpha-decarboxylation, an important pathway for degradation of phytanic acid in animals.
The results reported below show that the normal rat rapidly converts phytanic acid to its α-decarboxylation product, pristanic acid (2,6,10,14-tetramethylpentadecanoic acid). Expand
Refsum's disease--a recently characterized lipidosis involving the nervous system. Combined clinical staff conference at the National Institutes of Health.
Excerpt Dr. Daniel Steinberg: About the time of World War II, a young Norwegian neurologist, Sigvald Refsum, became intrigued with four patients referred to the Neurology Department of the Rikshosp...
The biosynthesis of lignoceric, cerebronic, and nervonic acids.
The lipids of the mammalian brain and nervous system are characterized in part by a relatively high content of CZ4 acids, which occur as important fatty acid components of the sphingolipids. TheExpand
Effect of prolonged fasting on the expired C14-O2 from palmitate and glucose in obese subjects.
Nine grossly obese patients were studied; first in the feeding state and then after a period of starvation, consistent with the hypothesis that in the starvation state the metabolism of fat continues at a more rapid rate than during feeding and that the metabolic rate of glucose tends to decrease. Expand
The mechanism of α-oxidation in leaves
Abstract 1. 1. The oxidation of [14C16]palmitate and of dl -2-hydroxy[14C16]palmitate by particulate fractions and by acetone-dried powders of young green leaves has been investigated. 2. 2.Expand
A pathway for oxidative degradation of phytanic acid in mammals.
Try, 0. Stokke, ibid
  • 1966