Refsum's disease: characterization of the enzyme defect in cell culture

Herndon, James H.; Steinberg, Daniel; Uhlendorf, B. William; Fales, Henry M.

doi:10.1172/jci106058

Cited by 119 publications

(36 citation statements)

References 47 publications

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“…Whereas 3-hydroxy-sebacic acid has been observed in defects of P-oxidation of medium-chain fatty acyl-CoA (12,24) and in ketoacidosis (25), the accumulation of 2-hydroxy-sebacic acid has not been reported in the urine of patients with inborn errors of metabolism. It may arise: 1) from the 2-hydroxylation and woxidation of LCFA and VLCFA and/or 2) from sebacic acid by analogy with the formation of 2-hydroxy-phytanic acid from phytanic acid in the liver (26). The 2-hydroxy-sebacic acid may further be degraded by oxidative decarboxylation, leading to azelaic and pimelic acids (Fig.…”

Section: Analysis and Quantitation Of Urinary Organic Acidsmentioning

confidence: 99%

Medium- and Long-Chain Dicarboxylic Aciduria in Patients with Zellweger Syndrome and Neonatal Adrenoleukodystrophy

1986

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ABSTRACT. This study reports that patients with neonatal adrenoleukodystrophy andIn rat liver, 6-oxidation of both VLCFA (1-3) and DA (4) occurs mostly in peroxisomes, only a minor fraction of these substrates being oxidized in mitochondria (3, 4).The accumulation of VLCFA in brain, adrenal glands, fibroblasts, and plasma of patients with ZS and NALD (5-8) have been attributed to a blockade of the peroxisomal oxidation of these fatty acids (3). We report here that odd-and even-numbered DA are excreted in excess in the urine of patients with ZS or NALD, which suggests that the peroxisomal and/or mitochondria1 P-oxidation of DA is also impaired.

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Section: Analysis and Quantitation Of Urinary Organic Acidsmentioning

confidence: 99%

Medium- and Long-Chain Dicarboxylic Aciduria in Patients with Zellweger Syndrome and Neonatal Adrenoleukodystrophy

1986

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“…Fibroblasts derived from skin punch biopsies were cultured by previously described techniques (20) in Eagle's minimal essential medium, modified to contain 0.16% NaHCOs, nonessential amino acids, neomycin (50 ,ug/ml), and 0.01%o Phenol Red (21,22) Co., Stamford, Conn.). Sonication at 2 A current was in six bursts of 5 sec each separated by 10-to 15-sec cooling periods.…”

Section: Metabolic Studiesmentioning

confidence: 99%

A defect in pyruvate decarboxylase in a child with an intermittent movement disorder

Blass¹,

Avigan²,

Uhlendorf³

1970

J. Clin. Invest.

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247

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“…This leads to the proposed pathway for degradation of phytanic acid shown in Figure 1. The occurrence of this pathway in man has been confirmed in tissue cultures of skin fibroblasts (3,7). The finding that i.v.…”

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confidence: 80%

“…The finding of severe phytanic acid accumulation combined with normal pristanic acid levels in plasma from such patients indicates that in these disorders the metabolic defect in the degradation pathway of phytanic acid is situated within its a-oxidation (10). In RD, a deficient a-hydroxylation of phytanic acid is supposed to be the only biochemical abnormality (7,8). In the rhizomelic form of CDP, an impaired plasmalogen biosynthesis and the occurrence of an unprocessed peroxisomal 3-oxoacylCoA thiolase are found next to an impaired phytanic acid aoxidation (1 1).…”

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confidence: 99%

In Vivo Study of Phytanic Acid α-Oxidation in Classic Refsum's Disease and Chondrodysplasia Punctata

et al. 1992

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ABSTRACT. A series of in vivo experiments is described in which [l-'3C]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 I3CO2 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 13COz were measured, whereas time-dependent analysis of labeled 2-hydroxyphytanic acid in plasma yielded a concentration curve superimposed upon the baseline value (0.2 pmollL) of the unlabeled substance. Phytanic acid accumulated in plasma from the Refsum's disease patient 1649 pmol/L, controls > 1 y (n = 100): c 10 pmol/L], whereas the pristanic acid concentration was within the control range 11.4 pmol/L, controls > 1 y (n = 100): c 3 pmol/L]. Low amounts of 2-hydroxyphytanic acid were found normally present 10.04 pmol/L, controls > 1 y (n = 11): < 0.2 pmol/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 pmol/L), the chondrodysplasia punctata patient showed an elevated 2-hydroxyphytanic acid plasma concentration (0.4 pmol/L), whereas the plasma pristanic acid level was in the control range (0.7 pmol/L). Oral administration of [l-I3C]phytanic acid (1 mg/kg body weight) to this patient resulted in a plasma concentration/time profile of labeled 2-hydroxyphytanic acid similar to that of the control. These findings demonstrate that a-hydroxylation of phytanic acid is a physiologic process and indicate that Refsum's disease and chondrodysplasia punctata patients have a different ability to convert phytanic acid into 2-hydroxyphytanic acid. (Pediatu Res 32: 566-570, 1992) Abbreviations CDP, chondrodysplasia punctata PFB, pentafluorobenzyl RCDP, rhizomelic chondrodysplasia punctata RD, Refsum's disease TMS, trimethylsilyl

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Refsum's disease: characterization of the enzyme defect in cell culture

Abstract: A B S T R A C T Refsum's disease (heredopathia atactica polyneuritiformis, HAP) is an inherited neurological disorder associated with storage of the branched-chain fatty acid, phytanic acid (3,7,11,15-tetramethylhexadecanoic acid

Cited by 119 publications

References 47 publications

Medium- and Long-Chain Dicarboxylic Aciduria in Patients with Zellweger Syndrome and Neonatal Adrenoleukodystrophy

Medium- and Long-Chain Dicarboxylic Aciduria in Patients with Zellweger Syndrome and Neonatal Adrenoleukodystrophy

A defect in pyruvate decarboxylase in a child with an intermittent movement disorder

In Vivo Study of Phytanic Acid α-Oxidation in Classic Refsum's Disease and Chondrodysplasia Punctata

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