Peroxisomal Disorders Treatment & Management

  • Author: Hoda Z Abdel-Hamid, MD; Chief Editor: Amy Kao, MD   more...
 
Updated: Jul 29, 2010
 

Medical Care

  • Management and treatment are based on the disorder, the age of onset, and the rate of progression as well the risks and benefits associated with the available therapies. Other considerations include parent expectations and the quality of life.
  • The treatment can be specific to the disorder, such as in the case of Refsum disease, which includes elimination of the toxic substance.
    • Because phytanic acid is exclusively of dietary origin (butter, cheese, beef, lamb, and some fish), its restriction can reduce its blood and tissue levels in 1-2 years.
    • Long-term follow-up has shown that dietary restriction improves peripheral-nerve and cardiac function and stabilizes the retinal abnormalities and hearing deficit.
    • In sick patients, phytanic acid levels can be rapidly lowered with plasma exchange; this may reverse some symptoms. Alternative means to decrease phytanic acid levels is w-oxidation by means of the cytochrome P-450 enzyme; however, this line of therapy remains experimental.
  • In patients with hyperoxaluria type I, combined liver-kidney transplantation has shown the greatest promise.
  • In patients with X-ALD, oral administration of a mixture of glyceryl trioleate and trierucate oils (also referred to as Lorenzo oil) normalizes levels of saturated VLCFA in plasma within 4 weeks. However, consider the following:
    • Clinical results in patients who already had neurologic involvement have been disappointing.
    • The therapy also does not appear to alter the rate of progression of endocrine abnormalities. However, it may diminish the frequency and severity of subsequent neurologic involvement, and it has been recommended in asymptomatic boys with X-ALD after the age of 1 year.
    • Bone marrow transplantation reversed neurologic, cognitive, and neuroradiological abnormalities in 1 patient who was treated when nervous-system involvement was still mild. Results in patients with advanced disease have been disappointing.
    • A French team has reported on autologous hematopoietic stem cell (HCT) gene therapy with a lentiviral vector in 2 patients with X-ALD. Progression of cerebral demyelination in the 2 patients began to stop 14-16 months after infusion of the genetically corrected cells, a clinical outcome comparable to that achieved by allogeneic HCT.[9]
    • Several laboratories are attempting to develop a genetic model of ADL in knock-out mice, with the aim of evaluating the efficacy of gene therapy.
    • Currently, HSCT is not indicated for AMN and Zellweger syndrome.[10]
  • Postnatal therapy of patients with disorders of peroxisome assembly is limited by the many abnormalities present at birth.
    • Recent data have demonstrated that patients with ZWS, NALD, and IRD have decreased blood tissue levels of docosahexanoic acid (DHA) and have suggested an important role of this substance in retina and brain. On this basis, Martinez et al initiated a therapeutic trial of this substance in patients with NALD. Improved visual and neurologic function was observed in 1 patient.[11]
    • Noguer and Martinez subsequently reported improved visual function with DHA ethyl ester treatment in 23 patients with peroxisomal disorders, 2 with classic Zellweger syndrome and 1 with D-bifunctional protein deficiency.[12]
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Contributor Information and Disclosures
Author

Hoda Z Abdel-Hamid, MD  Assistant Professor, Department of Pediatrics, Division of Child Neurology, University of Pittsburgh School of Medicine; Director of EMG Laboratory and Neuromuscular Program, Co-Director of MDA Clinic, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center

Hoda Z Abdel-Hamid, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Child Neurology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

David A Griesemer, MD  Professor, Departments of Neuroscience and Pediatrics, Medical University of South Carolina

David A Griesemer, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Epilepsy Society, Child Neurology Society, and Society for Neuroscience

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

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.

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: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Ortho McNeil Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Speaking, consulting

Chief Editor

Amy Kao, MD  Attending Neurologist, Children's National Medical Center, Washington DC

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society

Disclosure: Nothing to disclose.

References

  1. Wanders RJ. Peroxisomes, lipid metabolism, and human disease. Cell Biochem Biophys. 2000;32 Spring:89-106. [Medline].

  2. Wanders RJ, Ferdinandusse S, Brites P, Kemp S. Peroxisomes, lipid metabolism and lipotoxicity. Biochim Biophys Acta. Mar 2010;1801(3):272-80. [Medline].

  3. 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].

  4. 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].

  5. Kemp S, Wanders RJ. X-linked adrenoleukodystrophy: very long-chain fatty acid metabolism, ABC half-transporters and the complicated route to treatment. Mol Genet Metab. Mar 2007;90(3):268-76. [Medline].

  6. Semmler A, Bao X, Cao G, Köhler W, Weller M, Aubourg P, et al. Genetic variants of methionine metabolism and X-ALD phenotype generation: results of a new study sample. J Neurol. Aug 2009;256(8):1277-80. [Medline].

  7. Kaga M, Furushima W, Inagaki M, Nakamura M. Early neuropsychological signs of childhood adrenoleukodystrophy (ALD). Brain Dev. Aug 2009;31(7):558-61. [Medline].

  8. Hubbard WC, Moser AB, Liu AC, Jones RO, Steinberg SJ, Lorey F, et al. Newborn screening for X-linked adrenoleukodystrophy (X-ALD): validation of a combined liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. Mol Genet Metab. Jul 2009;97(3):212-20. [Medline].

  9. Cartier N, Hacein-Bey-Abina S, Bartholomae CC, Veres G, Schmidt M, Kutschera I, et al. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science. Nov 6 2009;326(5954):818-23. [Medline].

  10. Boelens JJ, Prasad VK, Tolar J, Wynn RF, Peters C. Current international perspectives on hematopoietic stem cell transplantation for inherited metabolic disorders. Pediatr Clin North Am. Feb 2010;57(1):123-45. [Medline].

  11. 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].

  12. Noguer MT, Martinez M. Visual Follow-Up In Peroxisomal-Disorder Patients Treated With Docosahexaenoic Acid Ethyl Ester. Invest Ophthalmol Vis Sci. Nov 20 2009;[Medline].

  13. 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].

  14. 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].

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

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

  17. 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].

  18. 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].

  19. 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].

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

  21. 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].

  22. 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].

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

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

  25. 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.

  26. 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].

  27. 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].

  28. 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].

  29. 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].

  30. 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].

  31. 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].

  32. 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].

  33. 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].

  34. 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].

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

  36. 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].

  37. 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].

  38. 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].

  39. 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].

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

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

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

  43. 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].

  44. 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].

  45. 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].

  46. 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].

  47. 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].

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

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

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

  51. 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].

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

  53. 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].

  54. 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].

  55. 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].

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

  57. 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].

  58. 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].

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

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

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

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

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

  64. 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].

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

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

 
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MRI of a patient with adrenoleukodystrophy showing the typical pattern of posterior white-matter involvement.
 
 
 
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