Cerebro-hepato-renal (Zellweger) syndrome, adrenoleukodystrophy, and Refsum's disease: Plasma changes and skin fibroblast phytanic acid oxidase

Poulos, A.; Sharp, P.; Fellenberg, A. J.; Danks, David M.

doi:10.1007/bf00273077

Cited by 64 publications

(39 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, phytanic acid oxidase [24,25], dihydroxyacetonephosphate acyltransferase [4,20,38] and lignoceric acid 13-oxidation activities [26] are deficient in cultured skin fibroblasts. In view of the biochemical [20,22,25,30,41], ultrastructural [13,14,19,29] and clinical similarities between Zellweger and infantile Refsum disease patients [2,4], it has been suggested that the defect in both conditions is similar or closely related [25], a hypothesis which has received strong support from recent somatic cell hybridization studies [40].…”

Section: Offprint Requests To: E F Robertsonmentioning

confidence: 98%

See 1 more Smart Citation

Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years

et al. 1988

Self Cite

View full text Add to dashboard Cite

Two patients with infantile phytanic acid storage disease (infantile Refsum disease), one of whom showed the presence of morphologically normal peroxisomes in a liver biopsy, were treated with a low phytanic acid diet for more than 2 years and the effects of treatment on certain clinical, biochemical and ultrastructural parameters were examined. Both patients showed evidence of either an improvement or stabilisation in their clinical condition. Plasma phytanic acid levels decreased to near normal values in approximately 6 weeks after the introduction of the diet; plasma pipecolic acid also declined markedly but the decrease was not so rapid and its level remained abnormal. C26:C22 fatty acid ratios decreased very slowly and even after 2 years the values remained grossly abnormal. Despite the marked reduction of phytanic acid in the liver, there was an increase in the C26:C22 fatty acid ratios and this appeared to be paralleled by an increase in inclusion bodies. Our data suggest that some patients with the infantile form of Refsum disease may show some clinical benefit from dietary management and this is reflected biochemically by decreases in the plasma levels of phytanic acid and pipecolic acid.

show abstract

Section: Offprint Requests To: E F Robertsonmentioning

confidence: 98%

“…Abbreviations: VLCFA = very long chain fatty acids; ALD = adrenoleukodystrophy blasts [22][23][24][25]36]. In addition, phytanic acid oxidase [24,25], dihydroxyacetonephosphate acyltransferase [4,20,38] and lignoceric acid 13-oxidation activities [26] are deficient in cultured skin fibroblasts.…”

Section: Offprint Requests To: E F Robertsonmentioning

confidence: 99%

Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years

et al. 1988

Self Cite

View full text Add to dashboard Cite

show abstract

“…This group of diseases is referred to as disorders of peroxisome biogenesis. Multiple biochemical abnormalities, including impaired beta-oxidation of very long chain fatty acids (VLCFA) (6), impaired oxidation of phytanic acid (7) and pipecolic acid (8), decreased plasmalogen synthesis (9), and abnormal bile acid metabolism (10) are observed in these generalized peroxisomal disorders. Clinically, infants with these disorders are characterized by severe hypotonia, early onset of seizures, and psychomotor retardation (2)(3)(4)(5)11).…”

Section: Introductionmentioning

confidence: 99%

Peroxisomal bifunctional enzyme deficiency.

et al. 1989

View full text Add to dashboard Cite

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.

show abstract

“…Similarly, the discovery that peroxisomes also catalyze the alpha-oxidation of fatty acids was based on the finding of greatly increased levels of phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) in plasma from Zellweger patients (Poulos et al 1985). Below, we will describe the major metabolic pathways in peroxisomes in humans and the interaction with other subcellular organelles.…”

Section: Metabolic Functions and Enzymology Of Peroxisomes In Humansmentioning

confidence: 98%

Peroxisomes in Humans: Metabolic Functions, Cross Talk with Other Organelles, and Pathophysiology of Peroxisomal Disorders

Wanders

Ferdinandusse

Waterham

2014

Molecular Machines Involved in Peroxisome Biogenesis and Maintenance

View full text Add to dashboard Cite

Peroxisomes play a crucial role in cellular metabolism as exemplified by the devastating consequences caused by deficiencies of one or more peroxisomal enzymes in humans. The major metabolic functions of peroxisomes in humans include fatty acid beta-oxidation, etherphospholipid biosynthesis, fatty acid alpha-oxidation; glyoxylate detoxification, bile acid synthesis, L-pipecolic acid oxidation, and docosahexaenoic acid (DHA) formation. Except from the bile acids which are true metabolic end products of bile acid formation in the liver as generated in peroxisomes, all the other products of peroxisome metabolism are not true end products but require continued metabolism in other organelles to reach their final fate. This explains the crosstalk between peroxisomes and other subcellular organelles notably mitochondria and the endoplasmic reticulum. In this review we will discuss the metabolic functions of peroxisomes in humans and the crosstalk with other subcellular organelles. In addition we will discuss the pathophysiological consequences of genetic defects in peroxisome metabolism.

show abstract

Cerebro-hepato-renal (Zellweger) syndrome, adrenoleukodystrophy, and Refsum's disease: Plasma changes and skin fibroblast phytanic acid oxidase

Cited by 64 publications

References 27 publications

Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years

Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years

Peroxisomal bifunctional enzyme deficiency.

Peroxisomes in Humans: Metabolic Functions, Cross Talk with Other Organelles, and Pathophysiology of Peroxisomal Disorders

Contact Info

Product

Resources

About