The Cerebrohepatorenal (Zellweger) Syndrome: An Improved Method for the Biochemical Diagnosis and its Potential Value for Prenatal Detection

Roscher, Adelbert A.; Molzer, Brunhilde; Bernheimer, H.; Stöckler, Sylvia; Mutz, I; Paltauf, Fritz

doi:10.1203/00006450-198509000-00013

Cited by 80 publications

(35 citation statements)

References 9 publications

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“…Oxidation assays for the branched-chain fatty acids phytanic acid and pristanic acid were carried out in cultured embryonic fibroblasts with [ (50). Plasmalogen synthesis activity was determined in the cultured MEFs by the double-substrate, double-isotope method (33).…”

Section: Measuring Peroxisome Abundancementioning

confidence: 99%

PEX11α Is Required for Peroxisome Proliferation in Response to 4-Phenylbutyrate but Is Dispensable for Peroxisome Proliferator-Activated Receptor Alpha-Mediated Peroxisome Proliferation

Li¹,

Baumgart²,

Dong

et al. 2002

Molecular and Cellular Biology

143

109

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The PEX11 peroxisomal membrane proteins promote peroxisome division in multiple eukaryotes. As part of our effort to understand the molecular and physiological functions of PEX11 proteins, we disrupted the mouse PEX11␣ gene. Overexpression of PEX11␣ is sufficient to promote peroxisome division, and a class of chemicals known as peroxisome proliferating agents (PPAs) induce the expression of PEX11␣ and promote peroxisome division. These observations led to the hypothesis that PPAs induce peroxisome abundance by enhancing PEX11␣ expression. The phenotypes of PEX11␣ ؊/؊ mice indicate that this hypothesis remains valid for a novel class of PPAs that act independently of peroxisome proliferator-activated receptor alpha (PPAR␣) but is not valid for the classical PPAs that act as activators of PPAR␣. Furthermore, we find that PEX11␣ ؊/؊ mice have normal peroxisome abundance and that cells lacking both PEX11␣ and PEX11␤, a second mammalian PEX11 gene, have no greater defect in peroxisome abundance than do cells lacking only PEX11␤. Finally, we report the identification of a third mammalian PEX11 gene, PEX11␥, and show that it too encodes a peroxisomal protein.

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Section: Measuring Peroxisome Abundancementioning

confidence: 99%

PEX11α Is Required for Peroxisome Proliferation in Response to 4-Phenylbutyrate but Is Dispensable for Peroxisome Proliferator-Activated Receptor Alpha-Mediated Peroxisome Proliferation

Li¹,

Baumgart²,

Dong

et al. 2002

Molecular and Cellular Biology

143

109

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“…Alpha-oxidation of [1-'4C]phytanic acid by cultured fibroblasts was measured by '4CO2 production as previously described (31). The peroxisomal steps of plasmalogen biosynthesis were assessed by the double-label, double-substrate method ofRoscher et al (32). Trihydroxycoprostanoic acid (THCA) concentration was determined by the method ofBjorkhem and Falk (33).…”

Section: Clinical Historymentioning

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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“…Concentrations of very long chain fatty acids in fibroblasts and plasma were measured by gas-liquid chromatography as previously described (26,27). The steps of plasmalogen biosynthesis in peroxisomes were assessed by the method of Roscher et al (28). This method uses a double-label, double-substrate incubation.…”

Section: Patient Selectionmentioning

confidence: 99%

Genetic and Phenotypic Heterogeneity in Disorders of Peroxisome Biogenesis—A Complementation Study Involving Cell Lines from 19 Patients

et al. 1989

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The Cerebrohepatorenal (Zellweger) Syndrome: An Improved Method for the Biochemical Diagnosis and its Potential Value for Prenatal Detection

Cited by 80 publications

References 9 publications

PEX11α Is Required for Peroxisome Proliferation in Response to 4-Phenylbutyrate but Is Dispensable for Peroxisome Proliferator-Activated Receptor Alpha-Mediated Peroxisome Proliferation

PEX11α Is Required for Peroxisome Proliferation in Response to 4-Phenylbutyrate but Is Dispensable for Peroxisome Proliferator-Activated Receptor Alpha-Mediated Peroxisome Proliferation

Peroxisomal bifunctional enzyme deficiency.

Genetic and Phenotypic Heterogeneity in Disorders of Peroxisome Biogenesis—A Complementation Study Involving Cell Lines from 19 Patients

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