Peroxisomal disorders

Current Opinion in Pediatrics

Volumn 11, Issue 6, 1999, Pages 572-576

  Raymond, Gerald V ^a  

^a KENNEDY KRIEGER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADRENOLEUKODYSTROPHY; ARTICLE; CATALASE DEFICIENCY; DISORDERS OF PEROXISOMAL FUNCTIONS; GENE MUTATION; GENE REARRANGEMENT; GENETIC LINKAGE; HUMAN; HYPEROXALURIA; PATHOGENESIS; PRIORITY JOURNAL; REFSUM DISEASE; ZELLWEGER SYNDROME;

ANIMALS; CHONDRODYSPLASIA PUNCTATA, RHIZOMELIC; HUMANS; MEMBRANE PROTEINS; MUTATION; PEROXISOMAL DISORDERS; ZELLWEGER SYNDROME;

EID: 0032725718     PISSN: 10408703     EISSN: None     Source Type: Journal    
DOI: 10.1097/00008480-199912000-00017     Document Type: Article

References (19)

1. Moser HW: Genotype-phenotype correlations in peroxisomal disorders. Dev Brain Dysfunction 1997, 10:282-292.
2. Lazarow PB, Moser HW: Disorders of peroxisomal biogenesis. In The Metabolic Basis of Inherited Disease, edn 7. Edited by Scriver CR, Beaudet AL, Sly WS, Valle D. New York: McGraw Hill; 1994:2287-2324.
3. Moser AB, Kreiter N, Bezman L, Lu S, Raymond GV, Naidu S, Moser HW: Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls. Ann Neurol 1999, 45:100-110.
4. Moser AB, Rasmussen M, Naidu S, Watkins PA, McGuinness M, Hajra AK, et al.: Phenotype of patients with peroxisomal disorders subdivided into sixteen complementation groups. J Pediatr 1995, 127:13-22.
5. Subramani S: PEX genes on the rise. Nat Genet 1997, 15:331-333.
6. Reuber BE, Germain-Lee E, Collins CS, Morrell JC, Ameritunga R, Moser HW, et al.: Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders. Nat Genet 1997, 17:445-448.
7. Geisbrecht BV, Collins CS, Reuber BE, Gould SJ: Disruption of a PEX1-PEX6 interaction is the most common cause of the neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease. Proc Natl Acad Sci U S A 1998, 95:8630-8635. •• The authors demonstrated that there is an important interaction of PEX1 and PEX6, that mutations interrupt that interaction, and that this failure is the single most common cause of peroxisome biogenesis defects resulting in the condition of Zellweger syndrome, NALD, and infantile Refsum disease.
8. Imamura A, Tamura S, Shimozawa N, Suzuki Y, Zhang Z, Tsukamoto T, et al.: Temperature-sensitive mutation in PEX1 moderates the phenotypes of peroxisome deficiency disorders. Hum Mol Genet 1998, 7:2089-2094.
9. Braverman N, Dodt G, Gould SJ, Valle D: An isoform of Pex5p, the human PTS1 receptor, is required for the import of PTS2 proteins into peroxisomes. Hum Mol Genet 1998, 7:1195-1205.
10. Braverman N, Dodt G, Gould SJ, Valle D: Disorders of peroxisome biogenesis. Hum Mol Genet 1995, 4:1791-1798.
11. Kunau WH, Erdmann R: Peroxisome biogenesis: back to the endoplasmic reticulum? Curr Biol 1998, 8:R299-R302. • This is a concise review of the role of the endoplasmic reticulum in the biogenesis of peroxisomes.
12. Noetzel MJ: Fish oil and myelin: cautious optimism for treatment of children with disorders of peroxisome biogenesis [editorial; comment]. Neurology 1998, 51:5-7. •• An excellent editorial that puts the use of DHA therapy in children with peroxisomal diseases in perspective. The lack of controlled trials in many rare inborn errors of metabolism must temper any conclusions about efficacy.
13. Martinez M, Vazquez E: MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders. Neurology 1998, 51:26-32. • The authors describe an interesting finding on magnetic resonance imaging in their open study of DHA therapy in children with peroxisomal biogenesis disorders. They state that there is an improvement in myelinization and hypothesize that the improvement is secondary to improved levels of DHA in oligodendrocytes or neurons. The study suffers, however, from the lack of a control group, and generalized statements about children with these disorders are not substantiated.
14. Moser HW: Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy [review]. Brain 1997, 120:1485-1508.
15. Korenke GC, Fuchs S, Krasemann E, Doerr HG, Wililchowski E, Hunneman DH, Hanefeld F: Cerebral adrenoleukodystrophy (ALD) in only one of monozygotic twins with an identical ALD genotype. Ann Neural 1996, 40:254-257.
16. Singh I, Pahan K, Khan M: Lovastatin and sodium phenylacetate normalize the levels of very long chain fatty acids in skin fibroblasts of X-adrenoleukodystrophy. FEBS Lett 1998, 426:342-346. • The authors demonstrate that the compounds lovastatin and phenylacetate not only restore the levels of VLCFAs to normal but in addition have actions that may have inhibit inflammation. The latter is thought to be a major component of the injury in the cerebral form of childhood ALD
17. Singh I, Khan M, Key L, Pai S: Lovastatin for X-linked adrenoleukodystrophy [letter]. N Engl J Med 1998, 339:702-703. • The authors state that in seven patients treated with 40 mg per day of lovastatin, a cholesterol-reducing medication, five had a lowering of VLCFAs. Two patients did not tolerate the therapy and discontinued treatment. The medication was used only for a limited period and no statements could be made as to clinical effect.
18. Kemp S, Wei HM, Lu JF, Braiterman LT, McGuinness MC, Moser AB, et al.: Gene redundancy and pharamacological gene therapy: implications for X-linked adrenoleukodystrophy. Nat Med 1998, 4:1261-1268. •• This paper is important not only for ALD but also for other peroxisomal diseases. Expanding on themes developed in other genetic diseases, the authors demonstrate that the butyrates, specifically 4-phenylbutyrate, by activating other genes may lead to pharmacologic gene therapy-the use of medications to turn on redundant genes at higher dosages and circumvent the disorder. Phenylbutyrate upregulates the ALDR gene, and this expression corrects the defect of VLCFA β oxidation in cultured fibroblast and in the ALD mouse. The unexpected increase in peroxisomes awaits further study but may have implications in other peroxisomal disorders.
19. Min K-T, Benzer S: Preventing neurodegeneration in the Drosophila mutant bubblegum. Science 1999, 284:1985-1988. •• A new use for fruit fly mutants in studying VLCFA oxidation defects. The bubblegum mutant has a defect in VLCFA acyl-coenzyme A synthetase, the initial step in peroxisomal β oxidation. What is impressive about this paper is the use of the flies not only in the demonstration of neurologic disease but also in the rapid evaluation of therapy. Preadults were treated with the monounsaturated glycerol trioleate, a component of Lorenzo's oil, and did not develop the disease.