eMedicine Specialties > Neurology > Pediatric Neurology

Peroxisomal Disorders: Follow-up

Author: Aziza Chedrawi, MD, Consultant, Department of Neurosciences, Section of Pediatric Neurology, King Faisal Specialist Hospital and Research Center
Coauthor(s): Gary D Clark, MD, Associate Professor of Pediatrics, Neurology, Chief of Neurophysiology, Chief of Pediatric Neurology, and Neurosciencediatrics, Baylor College of Medicine, Department of Pediatrics, Texas Children's Hospital
Contributor Information and Disclosures

Updated: Mar 8, 2007

Miscellaneous

Special Concerns

  • In the last few years, enormous progress has been mace in identifying and understanding the biochemical and genetic defects that underlie peroxisomal disorders.
    • Despite the identification of the genetic defects, the mechanisms by which they lead to abnormal morphogenesis and defective white-matter and neuronal degeneration are poorly understood.
    • Clarification of these processes is a major challenge for investigators.
    • Variations in phenotypic expression may be attributable to the action of other genes and/or unidentified environmental factors.
  • Human investigations, particularly static morphologic examinations of tissue at autopsy, have contributed immensely to the recognition and understanding of peroxisomal diseases. However, such studies continue to have significant limitations. The recently developed ZWS and ALD murine models may help clarify these poorly understood pathogenic mechanisms.
  • Prenatal diagnosis can be performed in all peroxisomal disorders.
 


More on Peroxisomal Disorders

Overview: Peroxisomal Disorders
Differential Diagnoses & Workup: Peroxisomal Disorders
Treatment & Medication: Peroxisomal Disorders
Follow-up: Peroxisomal Disorders
Multimedia: Peroxisomal Disorders
References
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References

  1. Aubourg P, Blanche S, Jambaque I, et al. Reversal of early neurologic and neuroradiologic manifestations of X-linked adrenoleukodystrophy by bone marrow transplantation. N Engl J Med. Jun 28 1990;322(26):1860-6. [Medline].

  2. Baes M, Gressens P, Baumgart E, et al. A mouse model for Zellweger syndrome. Nat Genet. Sep 1997;17(1):49-57. [Medline].

  3. Barker PB, Horska A. Neuroimaging in leukodystrophies. J Child Neurol. Aug 2004;19(8):559-70. [Medline].

  4. Barth PG, Majoie CB, Gootjes J, et al. Neuroimaging of peroxisome biogenesis disorders (Zellweger spectrum) with prolonged survival. Neurology. Feb 10 2004;62(3):439-44. [Medline].

  5. Baumgartner MR, Poll-The BT, Verhoeven NM, et al. Clinical approach to inherited peroxisomal disorders: a series of 27 patients. Ann Neurol. Nov 1998;44(5):720-30. [Medline].

  6. Bowen P, Lee CS, Zellweger H, Lindenberg R. A Familial Syndrome of Multiple Congenital Defects. Bull Johns Hopkins Hosp. Jun 1964;114:402-14. [Medline].

  7. Braverman N, Steel G, Obie C, et al. Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. Nat Genet. Apr 1997;15(4):369-76. [Medline].

  8. Breitling R. Pathogenesis of peroxisomal deficiency disorders (Zellweger syndrome) may be mediated by misregulation of the GABAergic system via the diazepam binding inhibitor. BMC Pediatr. Mar 12 2004;4:5. [Medline].

  9. Dimmick JE, Applegarth DA. Pathology of peroxisomal disorders. Perspect Pediatr Pathol. 1993;17:45-98. [Medline].

  10. Edwin D, Speedie LJ, Kohler W, et al. Cognitive and brain magnetic resonance imaging findings in adrenomyeloneuropathy. Ann Neurol. Oct 1996;40(4):675-8. [Medline].

  11. Esiri MM, Hyman NM, Horton WL, Lindenbaum RH. Adrenoleukodystrophy: clinical, pathological and biochemical findings in two brothers with the onset of cerebral disease in adult life. Neuropathol Appl Neurobiol. Nov-Dec 1984;10(6):429-45. [Medline].

  12. Ferri R, Chance PF. Lorenzo's oil: advances in the treatment of neurometabolic disorders. Arch Neurol. Jul 2005;62(7):1045-6. [Medline].

  13. Gartner J, Braun A, Holzinger A , et al. Clinical and genetic aspects of X-linked adrenoleukodystrophy. Neuropediatrics. Feb 1998;29(1):3-13. [Medline].

  14. Gilles L, Adams R, Kolony E. The neurology of neonatal hereditary metabolic diseases. In: Neurology of Hereditary Metabolic Diseases of Children. New York, NY: McGraw Hill;. 1996: 6-44.

  15. Griffin DE, Moser HW, Mendoza Q, et al. Identification of the inflammatory cells in the central nervous system of patients with adrenoleukodystrophy. Ann Neurol. Dec 1985;18(6):660-4. [Medline].

  16. Jaffe R, Crumrine P, Hashida Y, Moser HW. Neonatal adrenoleukodystrophy: clinical, pathologic, and biochemical delineation of a syndrome affecting both males and females. Am J Pathol. Jul 1982;108(1):100-11. [Medline].

  17. Jansen GA, Wanders RJ, Watkins PA,, Mihalik SJ. Phytanoyl-coenzyme A hydroxylase deficiency -- the enzyme defect in Refsum's disease. N Engl J Med. Jul 10 1997;337(2):133-4. [Medline].

  18. Jansen GA, Ofman R, Ferdinandusse S, et al. Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. Nat Genet. Oct 1997;17(2):190-3. [Medline].

  19. Jansen GA, Ofman R, Ferdinandusse S, et al. Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. Nat Genet. Oct 1997;17(2):190-3. [Medline].

  20. Kaufmann WE, Theda C, Naidu S, et al. Neuronal migration abnormality in peroxisomal bifunctional enzyme defect. Ann Neurol. Feb 1996;39(2):268-71. [Medline].

  21. Kelley RI, Datta NS, Dobyns WB, et al. Neonatal adrenoleukodystrophy: new cases, biochemical studies, and differentiation from Zellweger and related peroxisomal polydystrophy syndromes. Am J Med Genet. Apr 1986;23(4):869-901. [Medline].

  22. Knazek RA, Rizzo WB, Schulman JD, Dave JR. Membrane microviscosity is increased in the erythrocytes of patients with adrenoleukodystrophy and adrenomyeloneuropathy. J Clin Invest. Jul 1983;72(1):245-8. [Medline].

  23. Kruse B, Barker PB, van Zijl PC, et al. Multislice proton magnetic resonance spectroscopic imaging in X-linked adrenoleukodystrophy. Ann Neurol. Oct 1994;36(4):595-608. [Medline].

  24. Kumar AJ, Rosenbaum AE, Naidu S, et al. Adrenoleukodystrophy: correlating MR imaging with CT. Radiology. Nov 1987;165(2):497-504. [Medline].

  25. Lu JF, Lawler AM, Watkins PA, et al. A mouse model for X-linked adrenoleukodystrophy. Proc Natl Acad Sci U S A. Aug 19 1997;94(17):9366-71. [Medline].

  26. MacDonald JT, Stauffer AE, Heitoff K. Adrenoleukodystrophy: early frontal lobe involvement on computed tomography. J Comput Assist Tomogr. Feb 1984;8(1):128-30. [Medline].

  27. Martinez M, Pineda M, Vidal R, et al. Docosahexaenoic acid--a new therapeutic approach to peroxisomal-disorder patients: experience with two cases. Neurology. Jul 1993;43(7):1389-97. [Medline].

  28. McDonald JC, Landreneau MD, Rohr MS, DeVault GA Jr. Reversal by liver transplantation of the complications of primary hyperoxaluria as well as the metabolic defect. N Engl J Med. Oct 19 1989;321(16):1100-3. [Medline].

  29. Migeon BR, Moser HW, Moser AB, et al. Adrenoleukodystrophy: evidence for X linkage, inactivation, and selection favoring the mutant allele in heterozygous cells. Proc Natl Acad Sci U S A. Aug 1981;78(8):5066-70. [Medline].

  30. Mihalik SJ, Morrell JC, Kim D, et al. Identification of PAHX, a Refsum disease gene. Nat Genet. Oct 1997;17(2):185-9. [Medline].

  31. Moser HW, Naidu S, Kumar AJ, Rosenbaum AE. The adrenoleukodystrophies. Crit Rev Neurobiol. 1987;3(1):29-88. [Medline].

  32. Moser HW, Moser AB. Peroxisomal disorders: overview. Ann N Y Acad Sci. Dec 27 1996;804:427-41. [Medline].

  33. Moser HW, Raymond GV, Lu SE, et al. Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo's oil. Arch Neurol. Jul 2005;62(7):1073-80. [Medline].

  34. Mosser J, Douar AM, Sarde CO, et al. Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature. Feb 25 1993;361(6414):726-30. [Medline].

  35. Mosser J, Lutz Y, Stoeckel ME, et al. The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein. Hum Mol Genet. Feb 1994;3(2):265-71. [Medline].

  36. Ofman R, Hettema EH, Hogenhout EM, et al. Acyl-CoA:dihydroxyacetonephosphate acyltransferase: cloning of the human cDNA and resolution of the molecular basis in rhizomelic chondrodysplasia punctata type 2. Hum Mol Genet. May 1998;7(5):847-53. [Medline].

  37. Poll-The BT, Roels F, Ogier H, et al. A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy). Am J Hum Genet. Mar 1988;42(3):422-34. [Medline].

  38. Powers J. Peroxisomal diseases. In: Pediatric Neuropathology. Baltimore, Md: Lippincott Williams & Wilkins;. 1995: 630-9.

  39. Powers JM, Schaumburg HH, Johnson AB, Raine CS. A correlative study of the adrenal cortex in adreno-leukodystrophy--evidence for a fatal intoxication with very long chain saturated fatty acids. Invest Cell Pathol. Oct-Dec 1980;3(4):353-76. [Medline].

  40. Powers JM, Tummons RC, Caviness VS, et al. Structural and chemical alterations in the cerebral maldevelopment of fetal cerebro-hepato-renal (Zellweger) syndrome. J Neuropathol Exp Neurol. May 1989;48(3):270-89. [Medline].

  41. Powers JM, Liu Y, Moser AB, Moser HW. The inflammatory myelinopathy of adreno-leukodystrophy: cells, effector molecules, and pathogenetic implications. J Neuropathol Exp Neurol. Nov 1992;51(6):630-43. [Medline].

  42. Powers JM. The pathology of peroxisomal disorders with pathogenetic considerations. J Neuropathol Exp Neurol. Sep 1995;54(5):710-9. [Medline].

  43. Powers JM, Moser HW. Peroxisomal disorders: genotype, phenotype, major neuropathologic lesions, and pathogenesis. Brain Pathol. Jan 1998;8(1):101-20. [Medline].

  44. Powers JM. Adreno-leukodystrophy (adreno-testiculo-leukomyelo-neuropathic-complex). Clin Neuropathol. Sep-Oct 1985;4(5):181-99. [Medline].

  45. Purdue PE, Zhang JW, Skoneczny M, Lazarow PB. Rhizomelic chondrodysplasia punctata is caused by deficiency of human PEX7, a homologue of the yeast PTS2 receptor. Nat Genet. Apr 1997;15(4):381-4. [Medline].

  46. Roth KS. Peroxisomal disease--common ground for pediatrician, cell biologist, biochemist, pathologist, and neurologist. Clin Pediatr (Phila). Feb 1999;38(2):73-5. [Medline].

  47. Schram AW, Goldfischer S, van Roermund CW, et al. Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. Proc Natl Acad Sci U S A. Apr 1987;84(8):2494-6. [Medline].

  48. Volpe JJ, Adams RD. Cerebro-hepato-renal syndrome of Zellweger: an inherited disorder of neuronal migration. Acta Neuropathol (Berl). 1972;20(3):175-98. [Medline].

  49. Wanders RJ, Schutgens RB, Barth PG. Peroxisomal disorders: a review. J Neuropathol Exp Neurol. Sep 1995;54(5):726-39. [Medline].

  50. Wanders RJ. Peroxisomal disorders: clinical, biochemical, and molecular aspects. Neurochem Res. Apr 1999;24(4):565-80. [Medline].

  51. Wanders RJ. Metabolic and molecular basis of peroxisomal disorders: a review. Am J Med Genet A. May 1 2004;126(4):355-75. [Medline].

  52. Wanders RJ. Peroxisomes, lipid metabolism, and peroxisomal disorders. Mol Genet Metab. Sep-Oct 2004;83(1-2):16-27. [Medline].

  53. Wanders RJ, Waterham HR. Peroxisomal disorders I: biochemistry and genetics of peroxisome biogenesis disorders. Clin Genet. Feb 2005;67(2):107-33. [Medline].

  54. Watts RW, Morgan SH, Danpure CJ, et al. Combined hepatic and renal transplantation in primary hyperoxaluria type I: clinical report of nine cases. Am J Med. Feb 1991;90(2):179-88. [Medline].

  55. Yakovac WC. Calcareous chondropathies in the newborn infant. AMA Arch Pathol. Jan 1954;57(1):62-79. [Medline].

  56. Young RS, Ramer JC, Towfighi J, et al. Adrenoleukodystrophy: unusual computed tomographic appearance. Arch Neurol. Dec 1982;39(12):782-3. [Medline].

  57. al-Essa M, Dhaunsi GS, Rashed M, et al. Zellweger syndrome in Saudi Arabia and its distinct features. Clin Pediatr (Phila). Feb 1999;38(2):77-86. [Medline].

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Further Reading

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Keywords

disorders of peroxisomal biogenesis, PBD, disorders of peroxisomal beta-oxidation, POD, metabolic disorders, metabolic diseases, peroxisome disorders, peroxisome diseases, adrenoleukodystrophy, ALD, neonatal adrenoleukodystrophy, NALD, adrenomyeloneuropathy, infantile Refsum disease, IRD, hyperpipecolic acidemia, rhizomelic chondrodysplasia punctata, RCPD, pseudo–neonatal adrenoleukodystrophy, acyl CoA oxidase deficiency, metabolic kinase deficiency, hyperoxaluria type I, alanine glyoxylate aminotransferase deficiency, bifunctional enzyme deficiency, pseudo-Zellweger syndrome, peroxisome thiolase deficiency, acatalasemia, catalase deficiency, dihydroxy acetone phosphate acyltransferase deficiency, DHAP-AT, alkyl-DHAP synthase deficiency, glutaric aciduria, adult Refsum disease, ARD, classic Refsum disease, phytanoyl CoA hydroxylase deficiency, Zellweger syndrome, ZWS, microbody, microbodies, hyperpipecolic academia, HPA, cerebrohepatorenal syndrome, peroxisomal 2-methylacyl-CoA racemasedeficiency,AMACR, Lorenzo's oil

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Contributor Information and Disclosures

Author

Aziza Chedrawi, MD, Consultant, Department of Neurosciences, Section of Pediatric Neurology, King Faisal Specialist Hospital and Research Center
Aziza Chedrawi, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Coauthor(s)

Gary D Clark, MD, Associate Professor of Pediatrics, Neurology, Chief of Neurophysiology, Chief of Pediatric Neurology, and Neurosciencediatrics, Baylor College of Medicine, Department of Pediatrics, Texas Children's Hospital
Gary D Clark, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, Child Neurology Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

David A Griesemer, MD, Professor, Departments of Neurology and Pediatrics, Medical University of South Carolina
David A Griesemer, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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