Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Refsum Disease”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1979

Di-, mono- and nonphytanyl triglycerides in the serum: a sensitive parameter of the phytanic acid accumulation in Refsum's disease.

The relative proportions of the diphytanyl, monophytanyl and nonphytanyl triglycerides ("triglyceride pattern"), the phytanic acid content of the triglycerides and the phytanic acid levels in the serum of 3 patients with Refsum's disease (heredopathia atactica polyneuritiformis, phytanic acid storage disease) were estimated by thin-layer chromatography, densitometry and gas chromatography, respectively. The individual triglyceride patterns were clearly dependent on the phytanic acid content of the triglycerides: the more phytanic acid in the triglycerides, the higher the percentage of the diphytanyl and the lower the percentage of the nonphytanyl triglycerides. The monophytanyl triglycerides were also related to the phytanic acid content of the triglycerides, although in a complex manner. The triglyceride pattern can be taken as a parameter of the phytanic acid accumulation in Refsum's disease to be at least as sensitive as the serum phytanic acid level in the biochemical evaluation of the efficiency of the dietary treatment.

Eicosanoic Acids↗
PubMed1986

Accumulation and defective beta-oxidation of very long chain fatty acids in Zellweger's syndrome, adrenoleukodystrophy and Refsum's disease variants.

The accumulation of very long chain fatty acids in plasma and skin fibroblasts was measured in at least four separate inherited disease states. Both the magnitude and the nature of the fatty acid changes reflected the clinical status of individual patients. In Zellweger's syndrome, and to a lesser extent in infantile Refsum's disease, there was an increase in 24:0, 26:0, 26:1, and a number of even longer chain fatty acids, while in the X-linked form of adrenoleukodystrophy these changes were less pronounced. Zellweger fibroblasts in culture took up lignoceric, phytanic and stearic acids and incorporated them into a variety of lipids in a manner comparable to control fibroblasts. However, these cells were unable to convert phytanic or lignoceric acid to CO2. Infantile Refsum's and X-linked adrenoleukodystrophy fibroblasts showed normal conversion of these acids to CO2. Normal fibroblast homogenates produced radioactive acetate from [1-14C] stearic and [1-14C] lignoceric acids indicating that both substrates were beta-oxidised under these conditions. Homogenates of fibroblasts from all patients patients with biochemical evidence of accumulation of very long chain fatty acids showed normal or near-normal stearic acid beta-oxidation, but were deficient in lignoceric acid beta-oxidation. Residual lignoceric acid beta-oxidation activity varied from approximately 15% in Zellweger syndrome up to 50% in X-linked adrenoleukodystrophy. It is postulated that the accumulation of very long chain fatty acids results from defects in peroxisomal beta-oxidation. In Zellweger's syndrome, and possibly in infantile Refsum's disease, it is probable that this defect is secondary to a primary abnormality affecting the structure and/or function of peroxisomes, while the primary defect in X-linked adrenoleukodystrophy may be confined to a pathway specific for the oxidation of very long chain fatty acids.

Adrenoleukodystrophy↗
PubMed1988

[The kidney in Refsum's disease. Clinical, histologic and ultrastructural study of a case].

A renal biopsy was performed in a 41 year old man with Refsum's disease, following the onset of renal failure. 30% of the glomeruli were sclerosed, the others appeared normal. Ultrastructural examination revealed several types of inclusions within the tubular epithelial cells: dense bodies, simple or complex lipidic vacuoles and particularly structures composed of quadrangular microtubules with sides measuring 400 angstrom, rarely encountered in renal pathology. These dense elements, devoid of membrane and often in close contact with lipidic vacuoles, are found within the epithelial cells of the distal convoluted tubules and Henle's loops. They were localized extramitochondrially and no specimen was suggestive of a degraded form of the mitochondria. Some analogy can be made with the renal inclusions observed in Gaucher's disease.

Adult↗
PubMed1984

Patterns of Refsum's disease. Phytanic acid oxidase deficiency.

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 plasma phytanic acid value, generally considered to be pathognomonic for Refsum's disease (phytanic acid oxidase deficiency), was observed in three of these children but not in the fourth, who also showed no evidence of accumulation of phytanic acid in liver or fat biopsies. Our 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. Moreover, a failure to detect a raised plasma phytanic acid value may not necessarily indicate normal fibroblast phytanic acid oxidase activity.

Adult↗
PubMed1968

Lipid composition of the nervous system in Refsum's disease.

The compositions of the major lipids and their constituent fatty acids and fatty aldehydes from cerebral gray matter, white matter, and myelin, spinal cord myelin, and sciatic nerve were determined in a 57 yr old woman who died of Refsum's disease. There were deficiencies of ethanolamine glycerophosphatides (EGP) in gray matter and frontal lobe myelin, and a lipid with the chromatographic properties of lyso-EGP accumulated in all tissues. The proportions of the remaining lipids were nearly normal in the central nervous system tissues. In the sciatic nerve the proportions of sphingolipids were small; this observation is consistent with the severe demyelination noted on pathologic examination. Cholesteryl esters were not detected in any tissue. Phytanate (3,7,11,15-tetramethylhexadecanoate) was present in the glycerophosphatides from each tissue. Higher proportions of phytanate were found in choline glycerophosphatides (CGP) than in EGP or in serine glycerophosphatides (SGP). Hydrolysis with phospholipase established that phytanate was confined to the 1-position of CGP. More phytanate was found in CGP from myelin than from gray or white matter. Fourfold higher proportions of phytanate were found in CGP from sciatic nerve than in CGP from the central nervous system: in sciatic nerve, 24% of the fatty acids of CGP consisted of phytanate. The proportions and compositions of sphingolipid hydroxy fatty acids and odd-numbered fatty acids were normal in each tissue. These findings argue against a defect in sphingolipid alpha-hydroxy acid metabolism in Refsum's disease. The results are consistent with the view that the accumulation of phytanate is responsible for the demyelination.

Aldehydes↗
PubMed1985

Atypical phenotype of Refsum's disease: clinical, biochemical, neurophysiological and pathological study.

The authors describe the clinical, biochemical, electrophysiological and ultrastructural study of a case of Refsum's disease whose phenotype suggested other hereditary ataxias. Due to the presence of Babinski sign and optic atrophy and the absence of retinitis pigmentosa, this case can be considered atypical. Electrophysiological and ultrastructural findings confirm the variability of peripheral lesions in this hereditary polyneuropathy.

Adolescent↗
PubMed1982

[Refsum's disease: 10 years of a diet low in phytanic acid and phytol].

The authors report the evolution of two cases of Refsum's disease, treated with a specific phytol and phytanic acid diet for ten years. This treatment is effective leading to a rapid and stable fall of phytanemia, and a progressive improvement of the peripheral neuropathy and cerebellous symptoms, then prevent from quite new aggravation. Any symptom in favour of a cardiac, pulmonary or renal disease was observed during the past ten years. On the other hand, the sight and hearing disorders remained unchanged and are responsible to a major discomfort in this long-dated evolution. The strict liquid diet is quickly abandoned on account of a bad tolerance (diarrhea), but the ordinary diet is better endured, and is sufficient to keep a low phytanemia; this need a permanent continuation.

Adult↗
PubMed1992

In vivo study of phytanic acid alpha-oxidation in classic Refsum's disease and chondrodysplasia punctata.

A series of in vivo experiments is described in which [1-13C]phytanic acid was given as an oral substrate to a healthy subject and two patients showing an impairment in phytanic acid degradation, one with Refsum's disease and one with chondrodysplasia punctata. After intake of the substrate by the control in a dose of 20 mg/kg body weight, the production of 13CO2 was measured in exhaled breath air and the concomitant formation of labeled 2-hydroxyphytanic acid and of pristanic acid was demonstrated by plasma analysis. After application of a substrate dose of 1 mg/kg body weight to the control, no substantial amounts of 13CO2 were measured, whereas time-dependent analysis of labeled 2-hydroxyphytanic acid in plasma yielded a concentration curve superimposed upon the baseline value (0.2 mumol/L) of the unlabeled substance. Phytanic acid accumulated in plasma from the Refsum's disease patient [649 mumol/L, controls > 1 y (n = 100): < 10 mumol/L], whereas the pristanic acid concentration was within the control range [1.4 mumol/L, controls > 1 y (n = 100): < 3 mumol/L]. Low amounts of 2-hydroxyphytanic acid were found normally present [0.04 mumol/L, controls > 1 y (n = 11): < 0.2 mumol/L], and formation of labeled 2-hydroxyphytanic acid could not be demonstrated after ingestion of [1-13C]phytanic acid in a dose of 1 mg/kg body weight. In addition to phytanic acid accumulation (232 mumol/L), the chondrodysplasia punctata patient showed an elevated 2-hydroxyphytanic acid plasma concentration (0.4 mumol/L), whereas the plasma pristanic acid level was in the control range (0.7 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2006

CYP4 isoform specificity in the omega-hydroxylation of phytanic acid, a potential route to elimination of the causative agent of Refsum's disease.

The saturated C20 isoprenoid phytanic acid is physiologically derived from phytol released in the degradation of chlorophyll. The presence of a C-3 methyl group in this substrate blocks normal beta-oxidation, so phytanic acid degradation primarily occurs by initial peroxisomal alpha-oxidation to shift the register of the methyl group. However, individuals with Refsum's disease are genetically deficient in the required phytanoyl-CoA alpha-hydroxylase and suffer from neurological pathologies caused by the accumulation of phytanic acid. Recent work has shown that phytanic acid can also be catabolized by a pathway initiated by omega-hydroxylation of the hydrocarbon chain, followed by oxidation of the alcohol to the acid and conventional beta-oxidation. However, the enzymes responsible for the omega-hydroxylation of phytanic acid have not been identified. In this study, we have determined the activities of all of the rat and human CYP4A enzymes and two of the rat CYP4F enzymes, with respect to the omega-hydroxylation of phytanic acid. Furthermore, we have shown that the ability to omega-hydroxylate phytanic acid is elevated in microsomes from rats pretreated with clofibrate. The results support a possible role for CYP4 enzyme elevation in the elimination of phytanic acid in Refsum's disease patients.

Animals↗
PubMed1978

Occurrence of novel branched-chain fatty acids in Refsum's disease.

Two novel branched-chain fatty acids, which appear to be unsaturated analogs of phytanic acid, have been observed in sera and urine of patients with Refsum's disease. They occur in both phospholipids and neutral lipids, and have been isolated and characterized.

Eicosanoic Acids↗
PubMed1986

Rapid diagnosis of Zellweger syndrome and infantile Refsum's disease by fast atom bombardment--mass spectrometry of urine bile salts.

A method is described for the rapid determination of urinary bile salt profiles by fast atom bombardment--mass spectrometry (FAB-MS). Urine was passed through a reverse-phase octadecylsilane bonded silica cartridge and the bile salts eluted with methanol. Negative ion FAB spectra could be obtained from the equivalent of 10 microliter of urine loaded onto the target probe with glycerol as matrix. In samples from normal infants and children bile salt peaks were rarely detectable above the background whereas peaks produced by steroid sulphates and glucuronides and bile alcohol glucuronides could usually be identified. In samples from infants and children with cholestasis the major peaks were produced by the taurine and glycine conjugates of di-, tri- and tetrahydroxycholanoic acids (and their monosulphates). In samples from patients with Zellweger syndrome and infantile Refsum's disease, a unique ion at m/z 572 indicated the presence of taurine-conjugated tetrahydroxy-cholestanoic acid(s). The amide linkage to taurine was cleaved by alkaline hydrolysis but not by cholylglycine hydrolase. Capillary gas chromatography--mass spectrometry (GC-MS) of the bile acids liberated by alkaline hydrolysis indicated the presence of at least two nuclear-tetrahydroxylated cholestanoic acids, probably the 6 alpha- and 1 beta-hydroxylated derivatives of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid.

Bile Acids and Salts↗