Pseudo-Zellweger syndrome: Deficiencies in several peroxisomal oxidative activities

Goldfischer, Sidney; Collins, Janna C.; Rapin, Isabelle; Neumann, Paul E.; Neglia, Walter; Spiro, Alfred J.; Ishii, Tatsuya; Roels, Frank; Vamecq, Jòseph; Hoof, F. Van

doi:10.1016/s0022-3476(86)80764-8

Cited by 187 publications

(71 citation statements)

References 34 publications

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“…Goldfischer et al (17) reported a case in which peroxisomal beta-oxidation and bile acid metabolism were abnormal while peroxisome abundance, plasmalogen synthesis, and phytanic acid oxidation were normal. Subsequently, evidence was found for a deficiency of the peroxisomal beta-ketothiolase in postmortem liver from this patient (18).…”

Section: Introductionmentioning

confidence: 99%

Peroxisomal bifunctional enzyme deficiency.

et al. 1989

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Peroxisomal function was evaluated in a male infant with clinical features of neonatal adrenoleukodystrophy. Very long chain fatty acid levels were elevated in both plasma and fibroblasts, and beta-oxidation of very long chain fatty acids in cultured fibroblasts was significantly impaired. Although the level of the bile acid intermediate trihydroxycoprostanoic acid was slightly elevated in plasma, phytanic acid and L-pipecolic acid levels were normal, as was plasmalogen synthesis in cultured fibroblasts. The latter three parameters distinguish this case from classical neonatal adrenoleukodystrophy. In addition, electron microscopy and catalase subcellular distribution studies revealed that, in contrast to neonatal adrenoleukodystrophy, peroxisomes were present in the patient's tissues.Immunoblot studies of peroxisomal beta-oxidation enzymes revealed that the bifunctional enzyme (enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase) was deficient in postmortem liver samples, whereas acyl-CoA oxidase and the mature form of beta-ketothiolase were present. Density gradient centrifugation of fibroblast homogenates confirmed that intact peroxisomes were present. Immunoblots of fibroblast peroxisomal fractions showed that they contained acyl-CoA oxidase and beta-ketothiolase, but bifunctional enzyme was not detected. Northern analysis, however, revealed that mRNA coding for the bifunctional enzyme was present in the patient's fibroblasts.These results indicate that the primary biochemical defect in this patient is a deficiency of peroxisomal bifunctional enzyme. It is of interest that the phenotype of this patient resembled neonatal adrenoleukodystrophy and would not have been distinguished from this disorder by clinical study alone.

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Section: Introductionmentioning

confidence: 99%

Peroxisomal bifunctional enzyme deficiency.

et al. 1989

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“…The inborn errors ofbile acid synthesis described to date all affect side-chain oxidation (2)(3)(4)(5)(6)(7)(8), eg., cerebrotendinous xanthomatosis (2-5), Zellweger syndrome, infantile Refsum's disease, neonatal adrenoleukodystrophy (2,6), and pseudo-Zellweger syndrome (7).…”

Section: Introductionmentioning

confidence: 99%

Familial giant cell hepatitis associated with synthesis of 3 beta, 7 alpha-dihydroxy-and 3 beta,7 alpha, 12 alpha-trihydroxy-5-cholenoic acids.

Clayton¹,

Leonard²,

Lawson³

et al. 1987

J. Clin. Invest.

202

145

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Urinary bile acids from a 3-mo-old boy with cholestatic jaundice were analyzed by ion exchange chromatography and gas chromatography-mass spectrometry (GC-MS). This suggested the presence of labile sulfated cholenoic acids with an allylic hydroxyl group, a conclusion supported by analysis using fast atom bombardment mass spectrometry (FAB-MS). The compounds detected by FAB-MS were separated by thin layer chromatography and high performance liquid chromatography. The sulfated bile acids could be solvolyzed in acidified tetrahydrofuran, and glycine conjugates were partially hydrolyzed by cholylglycine hydrolase. Following solvolysis, deconjugation, and methylation with diazomethane, the bile acids were identified by GC-MS of trimethylsilyl derivatives. The major bile acids in the urine were 3,87a-dihydroxy-5-cholenoic acid 3-sulfate, 3#,7a,12a-tribydroxy-5-cholenoic acid monosulfate, and their glycine conjugates. Chenodeoxycholic acid and cholic acid were undetectable in urine and plasma. The family pedigree suggested that abnormal bile acid synthesis was an autosomal recessive condition leading to cirrhosis in early childhood.

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“…However, the strongly elevated concentration of plasma VLCFA and the elevated pristanic acid/phytanic acid ratio are suggestive of a defect in peroxisomal β-oxidation, as directly demonstrated by the deficient oxidation of C 26:0 and pristanic acid in cultured skin fibroblasts (Table 4). The normal profile of plasma bile acids (Table 2) suggests that bifunctional enzyme and peroxisomal thiolase are normally active, since patients with established deficiencies of these enzymes (Goldfischer et al 1986;Schram et al 1987;Watkins et al 1989) show at least slightly elevated concentrations of abnormal plasma bile acids (Table 5). Furthermore, an immunoblot analysis showed normal 41kDa thiolase, while the patient described by Goldfischer and colleagues (1986) showed absence of immunoreactive thiolase protein.…”

Section: New Peroxisomal Disorder 661mentioning

confidence: 99%

“…Goldfischer and colleagues (1986) were the first to report such a patient showing all the clinical signs and symptoms of Zellweger syndrome. Pseudo-Zellweger syndrome was the name given to the entity shown to be due to a deficiency of peroxisomal thiolase (Goldfischer et al 1986;Schram et al 1987). As the name indicates, the clinical symptoms were very similar to those seen in classical Zellweger patients.…”

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confidence: 96%