Skip to main content
NCBI home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1997 Jul;63(1):4–14. doi: 10.1136/jnnp.63.1.4

X linked adrenoleukodystrophy: clinical presentation, diagnosis, and therapy

B M van Geel 1, J Assies 1, R Wanders 1, P Barth 1
PMCID: PMC2169642  PMID: 9221959

Abstract

X linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal metabolism, biochemically characterised by accumulation of saturated very long chain fatty acids. Accumulation of these fatty acids is associated with cerebral demyelination, peripheral nerve abnormalities, and adrenocortical and testicular insufficiency. The lowest estimated birth incidence is one per 100 000. At least six phenotypes can be distinguished, of which the two most frequent are childhood cerebral ALD and adrenomyeloneuropathy. The X-ALD gene has been identified, but thus far no relation between genotype and phenotype has been found. Diagnosis is relatively easy and can be confirmed reliably, and prenatal testing is possible in affected families. Several therapeutic options, some with promising perspectives, are available. Neurologists and other physicians seem not to be familiar with the many facets of X-ALD. In this review, the clinical presentation, the relative frequencies of the different phenotypes, and the diagnostic and therapeutic options are presented.



Full Text

The Full Text of this article is available as a PDF (242.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angus B., de Silva R., Davidson R., Bone I. A family with adult-onset cerebral adrenoleucodystrophy. J Neurol. 1994 Jul;241(8):497–499. doi: 10.1007/BF00919712. [DOI] [PubMed] [Google Scholar]
  2. Asano J., Suzuki Y., Yajima S., Inoue K., Shimozawa N., Kondo N., Murase M., Orii T. Effects of erucic acid therapy on Japanese patients with X-linked adrenoleukodystrophy. Brain Dev. 1994 Nov-Dec;16(6):454–458. doi: 10.1016/0387-7604(94)90007-8. [DOI] [PubMed] [Google Scholar]
  3. Aubourg P., Adamsbaum C., Lavallard-Rousseau M. C., Lemaitre A., Boureau F., Mayer M., Kalifa G. Brain MRI and electrophysiologic abnormalities in preclinical and clinical adrenomyeloneuropathy. Neurology. 1992 Jan;42(1):85–91. doi: 10.1212/wnl.42.1.85. [DOI] [PubMed] [Google Scholar]
  4. Aubourg P., Adamsbaum C., Lavallard-Rousseau M. C., Rocchiccioli F., Cartier N., Jambaqué I., Jakobezak C., Lemaitre A., Boureau F., Wolf C. A two-year trial of oleic and erucic acids ("Lorenzo's oil") as treatment for adrenomyeloneuropathy. N Engl J Med. 1993 Sep 9;329(11):745–752. doi: 10.1056/NEJM199309093291101. [DOI] [PubMed] [Google Scholar]
  5. Aubourg P., Blanche S., Jambaqué I., Rocchiccioli F., Kalifa G., Naud-Saudreau C., Rolland M. O., Debré M., Chaussain J. L., Griscelli C. Reversal of early neurologic and neuroradiologic manifestations of X-linked adrenoleukodystrophy by bone marrow transplantation. N Engl J Med. 1990 Jun 28;322(26):1860–1866. doi: 10.1056/NEJM199006283222607. [DOI] [PubMed] [Google Scholar]
  6. Aubourg P., Sellier N., Chaussain J. L., Kalifa G. MRI detects cerebral involvement in neurologically asymptomatic patients with adrenoleukodystrophy. Neurology. 1989 Dec;39(12):1619–1621. doi: 10.1212/wnl.39.12.1619. [DOI] [PubMed] [Google Scholar]
  7. Bernheimer H., Budka H., Müller P. Brain tissue immunoglobulins in adrenoleukodystrophy: a comparison with multiple sclerosis and systemic lupus erythematosus. Acta Neuropathol. 1983;59(2):95–102. doi: 10.1007/BF00691593. [DOI] [PubMed] [Google Scholar]
  8. Blevins L. S., Jr, Shankroff J., Moser H. W., Ladenson P. W. Elevated plasma adrenocorticotropin concentration as evidence of limited adrenocortical reserve in patients with adrenomyeloneuropathy. J Clin Endocrinol Metab. 1994 Feb;78(2):261–265. doi: 10.1210/jcem.78.2.8106609. [DOI] [PubMed] [Google Scholar]
  9. Boué J., Oberle I., Heilig R., Mandel J. L., Moser A., Moser H., Larsen J. W., Jr, Dumez Y., Boué A. First trimester prenatal diagnosis of adrenoleukodystrophy by determination of very long chain fatty acid levels and by linkage analysis to a DNA probe. Hum Genet. 1985;69(3):272–274. doi: 10.1007/BF00293039. [DOI] [PubMed] [Google Scholar]
  10. Brown F. R., 3rd, Van Duyn M. A., Moser A. B., Schulman J. D., Rizzo W. B., Snyder R. D., Murphy J. V., Kamoshita S., Migeon C. J., Moser H. W. Adrenoleukodystrophy: effects of dietary restriction of very long chain fatty acids and of administration of carnitine and clofibrate on clinical status and plasma fatty acids. Johns Hopkins Med J. 1982 Oct;151(4):164–172. [PubMed] [Google Scholar]
  11. Budka H., Sluga E., Heiss W. D. Spastic paraplegia associated with Addison's disease: adult variant of adreno-leukodystrophy. J Neurol. 1976;213(3):237–250. doi: 10.1007/BF00312873. [DOI] [PubMed] [Google Scholar]
  12. Cappa M., Bertini E., del Balzo P., Cambiaso P., Di Biase A., Salvati S. High dose immunoglobulin IV treatment in adrenoleukodystrophy. J Neurol Neurosurg Psychiatry. 1994 Nov;57 (Suppl):69–71. doi: 10.1136/jnnp.57.suppl.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Carey W. F., Poulos A., Sharp P., Nelson P. V., Robertson E. F., Hughes J. L., Gill A. Pitfalls in the prenatal diagnosis of peroxisomal beta-oxidation defects by chorionic villus sampling. Prenat Diagn. 1994 Sep;14(9):813–819. doi: 10.1002/pd.1970140909. [DOI] [PubMed] [Google Scholar]
  14. Cartier N., Lopez J., Moullier P., Rocchiccioli F., Rolland M. O., Jorge P., Mosser J., Mandel J. L., Bougnères P. F., Danos O. Retroviral-mediated gene transfer corrects very-long-chain fatty acid metabolism in adrenoleukodystrophy fibroblasts. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1674–1678. doi: 10.1073/pnas.92.5.1674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chaudhry V., Moser H. W., Cornblath D. R. Nerve conduction studies in adrenomyeloneuropathy. J Neurol Neurosurg Psychiatry. 1996 Aug;61(2):181–185. doi: 10.1136/jnnp.61.2.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Costakos D., Abramson R. K., Edwards J. G., Rizzo W. B., Best R. G. Attitudes toward presymptomatic testing and prenatal diagnosis for adrenoleukodystrophy among affected families. Am J Med Genet. 1991 Dec 1;41(3):295–300. doi: 10.1002/ajmg.1320410307. [DOI] [PubMed] [Google Scholar]
  17. De Duve C., Baudhuin P. Peroxisomes (microbodies and related particles). Physiol Rev. 1966 Apr;46(2):323–357. doi: 10.1152/physrev.1966.46.2.323. [DOI] [PubMed] [Google Scholar]
  18. Dooley J. M., Wright B. A. Adrenoleukodystrophy mimicking multiple sclerosis. Can J Neurol Sci. 1985 Feb;12(1):73–74. doi: 10.1017/s0317167100046631. [DOI] [PubMed] [Google Scholar]
  19. Dumic M., Gubarev N., Sikic N., Roscher A., Plavsic V., Filipovic-Grcic B. Sparse hair and multiple endocrine disorders in two women heterozygous for adrenoleukodystrophy. Am J Med Genet. 1992 Jul 15;43(5):829–832. doi: 10.1002/ajmg.1320430515. [DOI] [PubMed] [Google Scholar]
  20. Elrington G. M., Bateman D. E., Jeffrey M. J., Lawton N. F. Adrenoleukodystrophy: heterogeneity in two brothers. J Neurol Neurosurg Psychiatry. 1989 Mar;52(3):310–313. doi: 10.1136/jnnp.52.3.310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Esiri M. M., Hyman N. M., Horton W. L., Lindenbaum R. H. Adrenoleukodystrophy: clinical, pathological and biochemical findings in two brothers with the onset of cerebral disease in adult life. Neuropathol Appl Neurobiol. 1984 Nov-Dec;10(6):429–445. doi: 10.1111/j.1365-2990.1984.tb00392.x. [DOI] [PubMed] [Google Scholar]
  22. FANCONI A., PRADER A., ISLER W., LUETHY F., SIEBENMANN R. MORBUS ADDISON MIT HIRNSKLEROSE IM KINDESALTER. EIN HEREDITAERES SYNDROM MIT X-CHROMOSOMALER VERERBUNG? Helv Paediatr Acta. 1963 Dec;18:480–501. [PubMed] [Google Scholar]
  23. Farrell D. F., Hamilton S. R., Knauss T. A., Sanocki E., Deeb S. S. X-linked adrenoleukodystrophy: adult cerebral variant. Neurology. 1993 Aug;43(8):1518–1522. doi: 10.1212/wnl.43.8.1518. [DOI] [PubMed] [Google Scholar]
  24. Feigenbaum V., Lombard-Platet G., Guidoux S., Sarde C. O., Mandel J. L., Aubourg P. Mutational and protein analysis of patients and heterozygous women with X-linked adrenoleukodystrophy. Am J Hum Genet. 1996 Jun;58(6):1135–1144. [PMC free article] [PubMed] [Google Scholar]
  25. Gray R. G., Green A., Cole T., Davidson V., Giles M., Schutgens R. B., Wanders R. J. A misdiagnosis of X-linked adrenoleukodystrophy in cultured chorionic villus cells by the measurement of very long chain fatty acids. Prenat Diagn. 1995 May;15(5):486–490. doi: 10.1002/pd.1970150514. [DOI] [PubMed] [Google Scholar]
  26. Green P. M. Chorea induced by oral contraceptives. Neurology. 1980 Oct;30(10):1131–1132. doi: 10.1212/wnl.30.10.1131. [DOI] [PubMed] [Google Scholar]
  27. Griffin D. E., Moser H. W., Mendoza Q., Moench T. R., O'Toole S., Moser A. B. Identification of the inflammatory cells in the central nervous system of patients with adrenoleukodystrophy. Ann Neurol. 1985 Dec;18(6):660–664. doi: 10.1002/ana.410180606. [DOI] [PubMed] [Google Scholar]
  28. Hashmi M., Stanley W., Singh I. Lignoceroyl-CoASH ligase: enzyme defect in fatty acid beta-oxidation system in X-linked childhood adrenoleukodystrophy. FEBS Lett. 1986 Feb 17;196(2):247–250. doi: 10.1016/0014-5793(86)80256-3. [DOI] [PubMed] [Google Scholar]
  29. Heffungs W., Hameister H., Ropers H. H. Addison disease and cerebral sclerosis in an apparently heterozygous girl: evidence for inactivation of the adrenoleukodystrophy locus. Clin Genet. 1980 Sep;18(3):184–188. doi: 10.1111/j.1399-0004.1980.tb00868.x. [DOI] [PubMed] [Google Scholar]
  30. Hruban Z., Vigil E. L., Slesers A., Hopkins E. Microbodies: constituent organelles of animal cells. Lab Invest. 1972 Aug;27(2):184–191. [PubMed] [Google Scholar]
  31. Igarashi M., Schaumburg H. H., Powers J., Kishmoto Y., Kolodny E., Suzuki K. Fatty acid abnormality in adrenoleukodystrophy. J Neurochem. 1976 Apr;26(4):851–860. doi: 10.1111/j.1471-4159.1976.tb04462.x. [DOI] [PubMed] [Google Scholar]
  32. Imamura A., Suzuki Y., Song X. Q., Fukao T., Shimozawa N., Orii T., Kondo N. Prenatal diagnosis of adrenoleukodystrophy by means of mutation analysis. Prenat Diagn. 1996 Mar;16(3):259–261. doi: 10.1002/(SICI)1097-0223(199603)16:3<259::AID-PD840>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  33. Jakobs B. S., Wanders R. J. Conclusive evidence that very-long-chain fatty acids are oxidized exclusively in peroxisomes in human skin fibroblasts. Biochem Biophys Res Commun. 1991 Aug 15;178(3):842–847. doi: 10.1016/0006-291x(91)90967-c. [DOI] [PubMed] [Google Scholar]
  34. James A. C., Kaplan P., Lees A., Bradley J. J. Schizophreniform psychosis and adrenomyeloneuropathy. J R Soc Med. 1984 Oct;77(10):882–884. doi: 10.1177/014107688407701015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Johnson A. B., Schaumburg H. H., Powers J. M. Histochemical characteristics of the striated inclusions of adrenoleukodystrophy. J Histochem Cytochem. 1976 Jun;24(6):725–730. doi: 10.1177/24.6.59773. [DOI] [PubMed] [Google Scholar]
  36. Jorge P., Quelhas D., Oliveira P., Pinto R., Nogueira A. X-linked adrenoleukodystrophy in patients with idiopathic Addison disease. Eur J Pediatr. 1994 Aug;153(8):594–597. doi: 10.1007/BF02190668. [DOI] [PubMed] [Google Scholar]
  37. Kemp S., Ligtenberg M. J., van Geel B. M., Barth P. G., Wolterman R. A., Schoute F., Sarde C. O., Mandel J. L., van Oost B. A., Bolhuis P. A. Identification of a two base pair deletion in five unrelated families with adrenoleukodystrophy: a possible hot spot for mutations. Biochem Biophys Res Commun. 1994 Jul 29;202(2):647–653. doi: 10.1006/bbrc.1994.1979. [DOI] [PubMed] [Google Scholar]
  38. Kemp S., Mooyer P. A., Bolhuis P. A., van Geel B. M., Mandel J. L., Barth P. G., Aubourg P., Wanders R. J. ALDP expression in fibroblasts of patients with X-linked adrenoleukodystrophy. J Inherit Metab Dis. 1996;19(5):667–674. doi: 10.1007/BF01799844. [DOI] [PubMed] [Google Scholar]
  39. Kennedy C. R., Allen J. T., Fensom A. H., Steinberg S. J., Wilson R. X-linked adrenoleukodystrophy with non-diagnostic plasma very long chain fatty acids. J Neurol Neurosurg Psychiatry. 1994 Jun;57(6):759–761. doi: 10.1136/jnnp.57.6.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Kishimoto Y., Moser H. W., Kawamura N., Platt M., Pallante S. L., Fenselau C. Adrenoleukodystrophy: evidence that abnormal very long chain fatty acids of brain cholesterol esters are of exogenous origin. Biochem Biophys Res Commun. 1980 Sep 16;96(1):69–76. doi: 10.1016/0006-291x(80)91182-1. [DOI] [PubMed] [Google Scholar]
  41. Kobayashi T., Noda S., Umezaki H., Goto I., Suzuki S., Kitaguchi T., Kuroiwa Y. Familial spinocerebellar degeneration as an expression of adrenoleukodystrophy. J Neurol Neurosurg Psychiatry. 1986 Dec;49(12):1438–1440. doi: 10.1136/jnnp.49.12.1438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Kok F., Neumann S., Sarde C. O., Zheng S., Wu K. H., Wei H. M., Bergin J., Watkins P. A., Gould S., Sack G. Mutational analysis of patients with X-linked adrenoleukodystrophy. Hum Mutat. 1995;6(2):104–115. doi: 10.1002/humu.1380060203. [DOI] [PubMed] [Google Scholar]
  43. Kong M. F., Jeffcoate W. Eighty-six cases of Addison's disease. Clin Endocrinol (Oxf) 1994 Dec;41(6):757–761. doi: 10.1111/j.1365-2265.1994.tb02790.x. [DOI] [PubMed] [Google Scholar]
  44. Korenke G. C., Christen H. J., Hunneman D. H., Hanefeld F. Failure of beta interferon therapy in X-linked adrenoleukodystrophy. Eur J Pediatr. 1996 Sep;155(9):833–833. doi: 10.1007/BF02002922. [DOI] [PubMed] [Google Scholar]
  45. Korenke G. C., Fuchs S., Krasemann E., Doerr H. G., Wilichowski E., Hunneman D. H., Hanefeld F. Cerebral adrenoleukodystrophy (ALD) in only one of monozygotic twins with an identical ALD genotype. Ann Neurol. 1996 Aug;40(2):254–257. doi: 10.1002/ana.410400221. [DOI] [PubMed] [Google Scholar]
  46. Korenke G. C., Hunneman D. H., Kohler J., Stöckler S., Landmark K., Hanefeld F. Glyceroltrioleate/glyceroltrierucate therapy in 16 patients with X-chromosomal adrenoleukodystrophy/adrenomyeloneuropathy: effect on clinical, biochemical and neurophysiological parameters. Eur J Pediatr. 1995 Jan;154(1):64–70. doi: 10.1007/BF01972976. [DOI] [PubMed] [Google Scholar]
  47. Krasemann E. W., Meier V., Korenke G. C., Hunneman D. H., Hanefeld F. Identification of mutations in the ALD-gene of 20 families with adrenoleukodystrophy/adrenomyeloneuropathy. Hum Genet. 1996 Feb;97(2):194–197. doi: 10.1007/BF02265264. [DOI] [PubMed] [Google Scholar]
  48. Krivit W., Lockman L. A., Watkins P. A., Hirsch J., Shapiro E. G. The future for treatment by bone marrow transplantation for adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy and Hurler syndrome. J Inherit Metab Dis. 1995;18(4):398–412. doi: 10.1007/BF00710052. [DOI] [PubMed] [Google Scholar]
  49. Kruse B., Barker P. B., van Zijl P. C., Duyn J. H., Moonen C. T., Moser H. W. Multislice proton magnetic resonance spectroscopic imaging in X-linked adrenoleukodystrophy. Ann Neurol. 1994 Oct;36(4):595–608. doi: 10.1002/ana.410360408. [DOI] [PubMed] [Google Scholar]
  50. Kumar A. J., Köhler W., Kruse B., Naidu S., Bergin A., Edwin D., Moser H. W. MR findings in adult-onset adrenoleukodystrophy. AJNR Am J Neuroradiol. 1995 Jun-Jul;16(6):1227–1237. [PMC free article] [PubMed] [Google Scholar]
  51. Kuroda S., Hirano A., Yuasa S. Adrenoleukodystrophy-cerebello-brainstem dominant case. Acta Neuropathol. 1983;60(1-2):149–152. doi: 10.1007/BF00685361. [DOI] [PubMed] [Google Scholar]
  52. Laureti S., Casucci G., Santeusanio F., Angeletti G., Aubourg P., Brunetti P. X-linked adrenoleukodystrophy is a frequent cause of idiopathic Addison's disease in young adult male patients. J Clin Endocrinol Metab. 1996 Feb;81(2):470–474. doi: 10.1210/jcem.81.2.8636252. [DOI] [PubMed] [Google Scholar]
  53. Lazo O., Contreras M., Hashmi M., Stanley W., Irazu C., Singh I. Peroxisomal lignoceroyl-CoA ligase deficiency in childhood adrenoleukodystrophy and adrenomyeloneuropathy. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7647–7651. doi: 10.1073/pnas.85.20.7647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Leiden J. M. Gene therapy--promise, pitfalls, and prognosis. N Engl J Med. 1995 Sep 28;333(13):871–873. doi: 10.1056/NEJM199509283331310. [DOI] [PubMed] [Google Scholar]
  55. Ligtenberg M. J., Kemp S., Sarde C. O., van Geel B. M., Kleijer W. J., Barth P. G., Mandel J. L., van Oost B. A., Bolhuis P. A. Spectrum of mutations in the gene encoding the adrenoleukodystrophy protein. Am J Hum Genet. 1995 Jan;56(1):44–50. [PMC free article] [PubMed] [Google Scholar]
  56. Loes D. J., Hite S., Moser H., Stillman A. E., Shapiro E., Lockman L., Latchaw R. E., Krivit W. Adrenoleukodystrophy: a scoring method for brain MR observations. AJNR Am J Neuroradiol. 1994 Oct;15(9):1761–1766. [PMC free article] [PubMed] [Google Scholar]
  57. Loes D. J., Stillman A. E., Hite S., Shapiro E., Lockman L., Latchaw R. E., Moser H., Krivit W. Childhood cerebral form of adrenoleukodystrophy: short-term effect of bone marrow transplantation on brain MR observations. AJNR Am J Neuroradiol. 1994 Oct;15(9):1767–1771. [PMC free article] [PubMed] [Google Scholar]
  58. Maestri N. E., Beaty T. H. Predictions of a 2-locus model for disease heterogeneity: application to adrenoleukodystrophy. Am J Med Genet. 1992 Nov 15;44(5):576–582. doi: 10.1002/ajmg.1320440509. [DOI] [PubMed] [Google Scholar]
  59. Maris T., Androulidakis E. J., Tzagournissakis M., Papavassiliou S., Moser H., Plaitakis A. X-linked adrenoleukodystrophy presenting as neurologically pure familial spastic paraparesis. Neurology. 1995 Jun;45(6):1101–1104. doi: 10.1212/wnl.45.6.1101. [DOI] [PubMed] [Google Scholar]
  60. Marsden C. D., Obeso J. A., Lang A. E. Adrenoleukomyeloneuropathy presenting as spinocerebellar degeneration. Neurology. 1982 Sep;32(9):1031–1032. doi: 10.1212/wnl.32.9.1031. [DOI] [PubMed] [Google Scholar]
  61. Martin J. J., Dompas B., Ceuterick C., Jacobs K. Adrenomyeloneuropathy and adrenoleukodystrophy in two brothers. Eur Neurol. 1980;19(5):281–287. doi: 10.1159/000115163. [DOI] [PubMed] [Google Scholar]
  62. Migeon B. R., Moser H. W., Moser A. B., Axelman J., Sillence D., Norum R. A. Adrenoleukodystrophy: evidence for X linkage, inactivation, and selection favoring the mutant allele in heterozygous cells. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5066–5070. doi: 10.1073/pnas.78.8.5066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Miike T., Taku K., Tamura T., Ohta J., Ozaki M., Yamamoto C., Sakai T., Antoku Y., Yadomi C. Clinical improvement of adrenoleukodystrophy following intravenous gammaglobulin therapy. Brain Dev. 1989;11(2):134–137. doi: 10.1016/s0387-7604(89)80083-x. [DOI] [PubMed] [Google Scholar]
  64. Molzer B., Bernheimer H., Toifl K. Fatty acid patterns in brain, fibroblast, leukocyte and body fluid lipids in adrenoleukodystrophy. Acta Neuropathol Suppl. 1981;7:211–214. doi: 10.1007/978-3-642-81553-9_63. [DOI] [PubMed] [Google Scholar]
  65. Moser A. B., Borel J., Odone A., Naidu S., Cornblath D., Sanders D. B., Moser H. W. A new dietary therapy for adrenoleukodystrophy: biochemical and preliminary clinical results in 36 patients. Ann Neurol. 1987 Mar;21(3):240–249. doi: 10.1002/ana.410210305. [DOI] [PubMed] [Google Scholar]
  66. Moser H. W., Bergin A., Naidu S., Ladenson P. W. Adrenoleukodystrophy. Endocrinol Metab Clin North Am. 1991 Jun;20(2):297–318. [PubMed] [Google Scholar]
  67. Moser H. W. Clinical and therapeutic aspects of adrenoleukodystrophy and adrenomyeloneuropathy. J Neuropathol Exp Neurol. 1995 Sep;54(5):740–745. doi: 10.1097/00005072-199509000-00017. [DOI] [PubMed] [Google Scholar]
  68. Moser H. W. Gene therapy in neurology. Eur Neurol. 1994;34(5):241–242. doi: 10.1159/000117050. [DOI] [PubMed] [Google Scholar]
  69. Moser H. W. Komrower Lecture. Adrenoleukodystrophy: natural history, treatment and outcome. J Inherit Metab Dis. 1995;18(4):435–447. doi: 10.1007/BF00710055. [DOI] [PubMed] [Google Scholar]
  70. Moser H. W., Moser A. B., Frayer K. K., Chen W., Schulman J. D., O'Neill B. P., Kishimoto Y. Adrenoleukodystrophy: increased plasma content of saturated very long chain fatty acids. Neurology. 1981 Oct;31(10):1241–1249. doi: 10.1212/wnl.31.10.1241. [DOI] [PubMed] [Google Scholar]
  71. Moser H. W., Moser A. B., Kawamura N., Murphy J., Suzuki K., Schaumburg H., Kishimoto Y. Adrenoleukodystrophy: elevated C26 fatty acid in cultured skin fibroblasts. Ann Neurol. 1980 Jun;7(6):542–549. doi: 10.1002/ana.410070607. [DOI] [PubMed] [Google Scholar]
  72. Moser H. W., Moser A. B., Naidu S., Bergin A. Clinical aspects of adrenoleukodystrophy and adrenomyeloneuropathy. Dev Neurosci. 1991;13(4-5):254–261. doi: 10.1159/000112170. [DOI] [PubMed] [Google Scholar]
  73. Moser H. W., Moser A. B., Powers J. M., Nitowsky H. M., Schaumburg H. H., Norum R. A., Migeon B. R. The prenatal diagnosis of adrenoleukodystrophy. Demonstration of increased hexacosanoic acid levels in cultured amniocytes and fetal adrenal gland. Pediatr Res. 1982 Mar;16(3):172–175. doi: 10.1203/00006450-198203000-00002. [DOI] [PubMed] [Google Scholar]
  74. Moser H. W., Moser A. B., Smith K. D., Bergin A., Borel J., Shankroff J., Stine O. C., Merette C., Ott J., Krivit W. Adrenoleukodystrophy: phenotypic variability and implications for therapy. J Inherit Metab Dis. 1992;15(4):645–664. doi: 10.1007/BF01799621. [DOI] [PubMed] [Google Scholar]
  75. Moser H. W., Moser A. E., Trojak J. E., Supplee S. W. Identification of female carriers of adrenoleukodystrophy. J Pediatr. 1983 Jul;103(1):54–59. doi: 10.1016/s0022-3476(83)80775-6. [DOI] [PubMed] [Google Scholar]
  76. Moser H. W., Tutschka P. J., Brown F. R., 3rd, Moser A. E., Yeager A. M., Singh I., Mark S. A., Kumar A. A., McDonnell J. M., White C. L., 3rd Bone marrow transplant in adrenoleukodystrophy. Neurology. 1984 Nov;34(11):1410–1417. doi: 10.1212/wnl.34.11.1410. [DOI] [PubMed] [Google Scholar]
  77. Mosser J., Douar A. M., Sarde C. O., Kioschis P., Feil R., Moser H., Poustka A. M., Mandel J. L., Aubourg P. Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature. 1993 Feb 25;361(6414):726–730. doi: 10.1038/361726a0. [DOI] [PubMed] [Google Scholar]
  78. Mosser J., Lutz Y., Stoeckel M. E., Sarde C. O., Kretz C., Douar A. M., Lopez J., Aubourg P., Mandel J. L. The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein. Hum Mol Genet. 1994 Feb;3(2):265–271. doi: 10.1093/hmg/3.2.265. [DOI] [PubMed] [Google Scholar]
  79. Naidu S., Bresnan M. J., Griffin D., O'Toole S., Moser H. W. Childhood adrenoleukodystrophy. Failure of intensive immunosuppression to arrest neurologic progression. Arch Neurol. 1988 Aug;45(8):846–848. doi: 10.1001/archneur.1988.00520320032011. [DOI] [PubMed] [Google Scholar]
  80. Notarangelo L. D., Parolini O., Baiguini G., Buzi F., Paterlini C., Perini A., Rimoldi M., Tiberti S., Uziel G., Notarangelo L. Carrier detection in X-linked adrenoleukodystrophy by determination of very long chain fatty acid levels and by linkage analysis. Eur J Pediatr. 1992 Oct;151(10):761–763. doi: 10.1007/BF01959086. [DOI] [PubMed] [Google Scholar]
  81. O'Neill B. P., Marmion L. C., Feringa E. R. The adrenoleukomyeloneuropathy complex: expression in four generations. Neurology. 1981 Feb;31(2):151–156. doi: 10.1212/wnl.31.2.151. [DOI] [PubMed] [Google Scholar]
  82. Paty D. W., Li D. K. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology. 1993 Apr;43(4):662–667. doi: 10.1212/wnl.43.4.662. [DOI] [PubMed] [Google Scholar]
  83. Phillips J. P., Lockman L. A., Shapiro E. G., Blazar B. R., Loes D. J., Moser H. W., Krivit W. CSF findings in adrenoleukodystrophy: correlation between measures of cytokines, IgG production, and disease severity. Pediatr Neurol. 1994 Jun;10(4):289–294. doi: 10.1016/0887-8994(94)90124-4. [DOI] [PubMed] [Google Scholar]
  84. Pilz P., Schiener P. Kombination von Morbus Addison und Morbus Schilder bei einer 43 jährigen Frau. Acta Neuropathol. 1973 Dec 3;26(4):357–360. doi: 10.1007/BF00688083. [DOI] [PubMed] [Google Scholar]
  85. Poulos A., Gibson R., Sharp P., Beckman K., Grattan-Smith P. Very long chain fatty acids in X-linked adrenoleukodystrophy brain after treatment with Lorenzo's oil. Ann Neurol. 1994 Nov;36(5):741–746. doi: 10.1002/ana.410360509. [DOI] [PubMed] [Google Scholar]
  86. Powers J. M. Adreno-leukodystrophy (adreno-testiculo-leukomyelo-neuropathic-complex). Clin Neuropathol. 1985 Sep-Oct;4(5):181–199. [PubMed] [Google Scholar]
  87. Powers J. M., Liu Y., Moser A. B., Moser H. W. The inflammatory myelinopathy of adreno-leukodystrophy: cells, effector molecules, and pathogenetic implications. J Neuropathol Exp Neurol. 1992 Nov;51(6):630–643. doi: 10.1097/00005072-199211000-00007. [DOI] [PubMed] [Google Scholar]
  88. Powers J. M., Schaumburg H. H. A fatal cause of sexual inadequacy in men: adreno-leukodystrophy. J Urol. 1980 Nov;124(5):583–585. doi: 10.1016/s0022-5347(17)55565-2. [DOI] [PubMed] [Google Scholar]
  89. Powers J. M., Schaumburg H. H. Adreno-leukodystrophy (sex-linked Schilder's disease). A pathogenetic hypothesis based on ultrastructural lesions in adrenal cortex, peripheral nerve and testis. Am J Pathol. 1974 Sep;76(3):481–491. [PMC free article] [PubMed] [Google Scholar]
  90. Powers J. M., Schaumburg H. H. The testis in adreno-leukodystrophy. Am J Pathol. 1981 Jan;102(1):90–98. [PMC free article] [PubMed] [Google Scholar]
  91. Rasmussen M., Moser A. B., Borel J., Khangoora S., Moser H. W. Brain, liver, and adipose tissue erucic and very long chain fatty acid levels in adrenoleukodystrophy patients treated with glyceryl trierucate and trioleate oils (Lorenzo's oil). Neurochem Res. 1994 Aug;19(8):1073–1082. doi: 10.1007/BF00968719. [DOI] [PubMed] [Google Scholar]
  92. Rizzo W. B., Leshner R. T., Odone A., Dammann A. L., Craft D. A., Jensen M. E., Jennings S. S., Davis S., Jaitly R., Sgro J. A. Dietary erucic acid therapy for X-linked adrenoleukodystrophy. Neurology. 1989 Nov;39(11):1415–1422. doi: 10.1212/wnl.39.11.1415. [DOI] [PubMed] [Google Scholar]
  93. Rizzo W. B., Phillips M. W., Dammann A. L., Leshner R. T., Jennings S. S., Avigan J., Proud V. K. Adrenoleukodystrophy: dietary oleic acid lowers hexacosanoate levels. Ann Neurol. 1987 Mar;21(3):232–239. doi: 10.1002/ana.410210304. [DOI] [PubMed] [Google Scholar]
  94. Rizzo W. B., Watkins P. A., Phillips M. W., Cranin D., Campbell B., Avigan J. Adrenoleukodystrophy: oleic acid lowers fibroblast saturated C22-26 fatty acids. Neurology. 1986 Mar;36(3):357–361. doi: 10.1212/wnl.36.3.357. [DOI] [PubMed] [Google Scholar]
  95. Sadeghi-Nejad A., Senior B. Adrenomyeloneuropathy presenting as Addison's disease in childhood. N Engl J Med. 1990 Jan 4;322(1):13–16. doi: 10.1056/NEJM199001043220103. [DOI] [PubMed] [Google Scholar]
  96. Schaumburg H. H., Powers J. M., Raine C. S., Spencer P. S., Griffin J. W., Prineas J. W., Boehme D. M. Adrenomyeloneuropathy: a probable variant of adrenoleukodystrophy. II. General pathologic, neuropathologic, and biochemical aspects. Neurology. 1977 Dec;27(12):1114–1119. doi: 10.1212/wnl.27.12.1114. [DOI] [PubMed] [Google Scholar]
  97. Schaumburg H. H., Powers J. M., Raine C. S., Suzuki K., Richardson E. P., Jr Adrenoleukodystrophy. A clinical and pathological study of 17 cases. Arch Neurol. 1975 Sep;32(9):577–591. doi: 10.1001/archneur.1975.00490510033001. [DOI] [PubMed] [Google Scholar]
  98. Schlote W., Molzer B., Peiffer J., Poremba M., Schumm F., Harzer K., Schnabel R., Bernheimer H. Adrenoleukodystrophy in an adult female. A clinical, morphological, and neurochemical study. J Neurol. 1987 Oct;235(1):1–9. doi: 10.1007/BF00314189. [DOI] [PubMed] [Google Scholar]
  99. Schäfer J. R., Ehlenz K., Steinmetz A., Pilz C., Hunneman D. H., Baerwald C., von Wichert P., Kaffarnik H. Adrenomyeloneuropathie. Eine häufige Ursache des Morbus Addison. Dtsch Med Wochenschr. 1994 Mar 11;119(10):327–331. doi: 10.1055/s-2008-1058698. [DOI] [PubMed] [Google Scholar]
  100. Sereni C., Paturneau-Jouas M., Aubourg P., Baumann N., Feingold J. Adrenoleukodystrophy in France: an epidemiological study. Neuroepidemiology. 1993;12(4):229–233. doi: 10.1159/000110321. [DOI] [PubMed] [Google Scholar]
  101. Sereni C., Ruel M., Iba-Zizen T., Baumann N., Marteau R., Paturneau-Jouas M. Adult adrenoleukodystrophy: a sporadic case? J Neurol Sci. 1987 Sep;80(2-3):121–128. doi: 10.1016/0022-510x(87)90148-1. [DOI] [PubMed] [Google Scholar]
  102. Shapiro E. G., Lockman L. A., Balthazor M., Krivit W. Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation. J Inherit Metab Dis. 1995;18(4):413–429. doi: 10.1007/BF00710053. [DOI] [PubMed] [Google Scholar]
  103. Simpson R. H., Rodda J., Reinecke C. J. Adrenoleukodystrophy in a mother and son. J Neurol Neurosurg Psychiatry. 1987 Sep;50(9):1165–1172. doi: 10.1136/jnnp.50.9.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Singh I., Moser A. E., Goldfischer S., Moser H. W. Lignoceric acid is oxidized in the peroxisome: implications for the Zellweger cerebro-hepato-renal syndrome and adrenoleukodystrophy. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4203–4207. doi: 10.1073/pnas.81.13.4203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. Sobue G., Ueno-Natsukari I., Okamoto H., Connell T. A., Aizawa I., Mizoguchi K., Honma M., Ishikawa G., Mitsuma T., Natsukari N. Phenotypic heterogeneity of an adult form of adrenoleukodystrophy in monozygotic twins. Ann Neurol. 1994 Dec;36(6):912–915. doi: 10.1002/ana.410360617. [DOI] [PubMed] [Google Scholar]
  106. Stumpf D. A., Hayward A., Haas R., Frost M., Schaumburg H. H. Adrenoleukodystrophy. Failure of immunosuppression to prevent neurological progression. Arch Neurol. 1981 Jan;38(1):48–49. doi: 10.1001/archneur.1981.00510010074014. [DOI] [PubMed] [Google Scholar]
  107. Stöckler S., Millner M., Molzer B., Ebner F., Körner E., Moser H. W. Multiple sclerosis-like syndrome in a woman heterozygous for adrenoleukodystrophy. Eur Neurol. 1993;33(5):390–392. doi: 10.1159/000116978. [DOI] [PubMed] [Google Scholar]
  108. Stöckler S., Molzer B., Plecko B., Zenz W., Muntean W., Söling U., Hunneman D. H., Korenke C., Hanefeld F. Giant platelets in erucic acid therapy for adrenoleukodystrophy. Lancet. 1993 May 29;341(8857):1414–1415. doi: 10.1016/0140-6736(93)90984-o. [DOI] [PubMed] [Google Scholar]
  109. Toplak H., Wascher T. C., Pleschko B., Ramschak H., Sedlmayr P., Wilders-Truschnigg M., Stöckler S. Reduced stimulability of platelet surface adhesion molecules under treatment with Lorenzo's oil. J Inherit Metab Dis. 1994;17(5):628–629. doi: 10.1007/BF00711605. [DOI] [PubMed] [Google Scholar]
  110. Tsuji S., Sano T., Ariga T., Miyatake T. Increased synthesis of hexacosanoic acid (C23:0) by cultured skin fibroblasts from patients with adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN). J Biochem. 1981 Oct;90(4):1233–1236. doi: 10.1093/oxfordjournals.jbchem.a133578. [DOI] [PubMed] [Google Scholar]
  111. Tsuji S., Suzuki M., Ariga T., Sekine M., Kuriyama M., Miyatake T. Abnormality of long-chain fatty acids in erythrocyte membrane sphingomyelin from patients with adrenoleukodystrophy. J Neurochem. 1981 Mar;36(3):1046–1049. doi: 10.1111/j.1471-4159.1981.tb01698.x. [DOI] [PubMed] [Google Scholar]
  112. Uziel G., Bertini E., Bardelli P., Rimoldi M., Gambetti M. Experience on therapy of adrenoleukodystrophy and adrenomyeloneuropathy. Dev Neurosci. 1991;13(4-5):274–279. doi: 10.1159/000112173. [DOI] [PubMed] [Google Scholar]
  113. Valle D., Gärtner J. Human genetics. Penetrating the peroxisome. Nature. 1993 Feb 25;361(6414):682–683. doi: 10.1038/361682a0. [DOI] [PubMed] [Google Scholar]
  114. Wanders R. J., Heymans H. S., Schutgens R. B., Barth P. G., van den Bosch H., Tager J. M. Peroxisomal disorders in neurology. J Neurol Sci. 1988 Dec;88(1-3):1–39. doi: 10.1016/0022-510x(88)90203-1. [DOI] [PubMed] [Google Scholar]
  115. Wanders R. J., Schutgens R. B., Barth P. G., Tager J. M., van den Bosch H. Postnatal diagnosis of peroxisomal disorders: a biochemical approach. Biochimie. 1993;75(3-4):269–279. doi: 10.1016/0300-9084(93)90087-9. [DOI] [PubMed] [Google Scholar]
  116. Wanders R. J., Schutgens R. B., van den Bosch H., Tager J. M., Kleijer W. J. Prenatal diagnosis of inborn errors in peroxisomal beta-oxidation. Prenat Diagn. 1991 Apr;11(4):253–261. doi: 10.1002/pd.1970110407. [DOI] [PubMed] [Google Scholar]
  117. Wanders R. J., van Roermund C. W., Lageweg W., Jakobs B. S., Schutgens R. B., Nijenhuis A. A., Tager J. M. X-linked adrenoleukodystrophy: biochemical diagnosis and enzyme defect. J Inherit Metab Dis. 1992;15(4):634–644. doi: 10.1007/BF01799620. [DOI] [PubMed] [Google Scholar]
  118. Wanders R. J., van Roermund C. W., van Wijland M. J., Nijenhuis A. A., Tromp A., Schutgens R. B., Brouwer-Kelder E. M., Schram A. W., Tager J. M., van den Bosch H. X-linked adrenoleukodystrophy: defective peroxisomal oxidation of very long chain fatty acids but not of very long chain fatty acyl-CoA esters. Clin Chim Acta. 1987 Jun 15;165(2-3):321–329. doi: 10.1016/0009-8981(87)90177-x. [DOI] [PubMed] [Google Scholar]
  119. Watkins P. A., Gould S. J., Smith M. A., Braiterman L. T., Wei H. M., Kok F., Moser A. B., Moser H. W., Smith K. D. Altered expression of ALDP in X-linked adrenoleukodystrophy. Am J Hum Genet. 1995 Aug;57(2):292–301. [PMC free article] [PubMed] [Google Scholar]
  120. Weller M., Liedtke W., Petersen D., Opitz H., Poremba M. Very-late-onset adrenoleukodystrophy: possible precipitation of demyelination by cerebral contusion. Neurology. 1992 Feb;42(2):367–370. doi: 10.1212/wnl.42.2.367. [DOI] [PubMed] [Google Scholar]
  121. Whitcomb R. W., Linehan W. M., Knazek R. A. Effects of long-chain, saturated fatty acids on membrane microviscosity and adrenocorticotropin responsiveness of human adrenocortical cells in vitro. J Clin Invest. 1988 Jan;81(1):185–188. doi: 10.1172/JCI113292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  122. Wilkinson I. A., Hopkins I. J., Pollard A. C. Can head injury influence the site of demyelination in adrenoleukodystrophy? Dev Med Child Neurol. 1987 Dec;29(6):797–800. doi: 10.1111/j.1469-8749.1987.tb08827.x. [DOI] [PubMed] [Google Scholar]
  123. Zierz S., Schröder R., Unkrig C. J. Thrombocytopenia induced by erucic acid therapy in patients with X-linked adrenoleukodystrophy. Clin Investig. 1993 Oct;71(10):802–805. doi: 10.1007/BF00190322. [DOI] [PubMed] [Google Scholar]
  124. Zinkham W. H., Kickler T., Borel J., Moser H. W. Lorenzo's oil and thrombocytopenia in patients with adrenoleukodystrophy. N Engl J Med. 1993 Apr 15;328(15):1126–1127. doi: 10.1056/NEJM199304153281513. [DOI] [PubMed] [Google Scholar]
  125. van Geel B. M., Assies J., Haverkort E. B., Barth P. G., Wanders R. J., Schutgens R. B., Keyser A., Zwetsloot C. P. Delay in diagnosis of X-linked adrenoleukodystrophy. Clin Neurol Neurosurg. 1993 Jun;95(2):115–120. doi: 10.1016/0303-8467(93)90004-z. [DOI] [PubMed] [Google Scholar]
  126. van Geel B. M., Assies J., Weverling G. J., Barth P. G. Predominance of the adrenomyeloneuropathy phenotype of X-linked adrenoleukodystrophy in The Netherlands: a survey of 30 kindreds. Neurology. 1994 Dec;44(12):2343–2346. doi: 10.1212/wnl.44.12.2343. [DOI] [PubMed] [Google Scholar]
  127. van Geel B. M., Koelman J. H., Barth P. G., Ongerboer de Visser B. W. Peripheral nerve abnormalities in adrenomyeloneuropathy: a clinical and electrodiagnostic study. Neurology. 1996 Jan;46(1):112–118. doi: 10.1212/wnl.46.1.112. [DOI] [PubMed] [Google Scholar]
  128. van Oost B. A., van Zandvoort P. M., Tünte W., Brunner H. G., Hoogeboom A. J., Maaswinkel-Mooy P. D., Bakkeren J., Hamel B., Ropers H. H. Linkage analysis in X-linked adrenoleukodystrophy and application in post- and prenatal diagnosis. Hum Genet. 1991 Feb;86(4):404–407. doi: 10.1007/BF00201845. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES