Skip to main content

Advertisement

SpringerLink
Log in

X-Linked Adrenoleukodystrophy: Pathogenesis and Treatment

  • Demyelinating Disorders (DN Bourdette and V Yadav, Section Editors)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

X-linked adrenoleukodystrophy (X-ALD) is a puzzling inborn error of metabolism with a strikingly heterogeneous clinical spectrum. All patients have mutations in the ABCD1 gene and accumulate very long chain fatty acids in all tissues. Virtually all male X-ALD patients develop adrenocortical insufficiency in childhood and progressive myelopathy and peripheral neuropathy in adulthood. A subset of male patients, however, develops a fatal cerebral demyelinating disease, cerebral adrenoleukodystrophy. Female patients also develop progressive myelopathy and peripheral neuropathy, but generally at a later age than males. They only very rarely develop adrenocortical insufficiency or cerebral adrenoleukodystrophy. This review proposes to simplify the classification of the clinical spectrum of X-ALD and reviews the largely unresolved pathophysiological mechanisms and the current treatment options.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Heubner O. Über diffuse Hirnsclerose. Charite Ann. 1897;22:298–310.

    Google Scholar 

  2. Haberfield W, Spieler F. Zur diffusen Hirn-Ruckenmarksklerose im Kindesalter. Dt Z Nervheilk. 1910;40:436–63.

    Article  Google Scholar 

  3. Siemerling E, Creutzfeldt HG. Bronzekrankheit und sklerosierende Enzephalomyelitis. Arch Psychiat Nervenkr. 1923;68:217–44.

    Article  Google Scholar 

  4. Schilder PF. Zur Frage der Encephalitis periaxialis diffusa (sogenannten diffusen Sklerose). Z Gesamte Neurol Psychiatry. 1913;15:359–76.

    Article  Google Scholar 

  5. Schilder PF. Die Encephalitis periaxialis diffusa (nebst Bemerkungen über die Apraxie des Lidschlusses). Arch Psychiatr Nervenkr. 1924;71:327–56.

    Article  Google Scholar 

  6. Adams RD, Kubik CS. The morbid anatomy of the demyelinative disease. Am J Med. 1952;12(5):510–46.

    Article  PubMed  CAS  Google Scholar 

  7. Hoefnagel D, Brun A, Ingbar SH. Addison’s disease and diffuse cerebral sclerosis. J Neurol Neurosurg Psychiatry. 1967;30(1):56–60.

    Article  PubMed Central  Google Scholar 

  8. Hoefnagel D, Van Den Noort S, Ingbar SH. Diffuse cerebral sclerosis with endocrine abnormalities in young males. Brain. 1962;85:553–68.

    Article  PubMed  CAS  Google Scholar 

  9. Fanconi A, Prader A, Isler W, Luethy F, Siebenmann R. Addison’s disease with cerebral sclerosis in childhood. A hereditary syndrome transmitted through chromosome X? Helv Paediatr Acta. 1963;18:480–501.

    PubMed  CAS  Google Scholar 

  10. Blaw ME, Osterberg K, Kozak P, Nelson E. Sudanophilic leukodystrophy and adrenal cortical atrophy. Arch Neurol. 1964;11:626–31.

    Article  PubMed  CAS  Google Scholar 

  11. Crome L, Zapella M. Schilder’s Disease (Sudanophilic leucodystrophy) in five male members of one family. J Neurol Neurosurg Psychiatry. 1963;26:431–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Blaw ME. Melanodermic type leukodystrophy (adreno-leukodystrophy). In: Vinken PJ, Bruyn CW, editors. Handbook of clinical neurology. New York: American Elsevier; 1970. p. 128–33.

    Google Scholar 

  13. Powers JM, Schaumburg HH. 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;76(3):481–91.

    PubMed  CAS  PubMed Central  Google Scholar 

  14. Igarashi M, Schaumburg HH, Powers J, Kishmoto Y, Kolodny E, Suzuki K. Fatty acid abnormality in adrenoleukodystrophy. J Neurochem. 1976;26(4):851–60.

    Article  PubMed  CAS  Google Scholar 

  15. Penman RW. Addison’s disease in association with spastic paraplegia. Br Med J. 1960;1(5170):402.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Harris-Jones JN, Nixon PG. Familial Addison’s disease with spastic paraplegia. J Clin Endocrinol Metab. 1955;15(6):739–44. doi:10.1210/jcem-15-6-739.

    Article  PubMed  CAS  Google Scholar 

  17. Griffin JW, Goren E, Schaumburg H, Engel WK, Loriaux L. Adrenomyeloneuropathy: a probable variant of adrenoleukodystrophy. I. Clinical and endocrinologic aspects. Neurology. 1977;27(12):1107–13.

    Article  PubMed  CAS  Google Scholar 

  18. Schaumburg HH, Powers JM, Raine CS, Spencer PS, Griffin JW, Prineas JW, et al. Adrenomyeloneuropathy: a probable variant of adrenoleukodystrophy. II. General pathologic, neuropathologic, and biochemical aspects. Neurology. 1977;27(12):1114–9.

    Article  PubMed  CAS  Google Scholar 

  19. Budka H, Sluga E, Heiss WD. Spastic paraplegia associated with Addison’s disease: adult variant of adreno-leukodystrophy. J Neurol. 1976;213(3):237–50.

    Article  PubMed  CAS  Google Scholar 

  20. Migeon BR, Moser HW, Moser AB, Axelman J, Sillence D, Norum RA. Adrenoleukodystrophy: evidence for X linkage, inactivation, and selection favoring the mutant allele in heterozygous cells. Proc Natl Acad Sci U S A. 1981;78(8):5066–70.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Mosser J, Douar AM, Sarde CO, Kioschis P, Feil R, Moser H, et al. Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature. 1993;361(6414):726–30. doi:10.1038/361726a0.

    Article  PubMed  CAS  Google Scholar 

  22. Mosser J, Lutz Y, Stoeckel ME, Sarde CO, Kretz C, Douar AM, et al. The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein. Hum Mol Genet. 1994;3(2):265–71.

    Article  PubMed  CAS  Google Scholar 

  23. Moser HW, Smith KD, Watkins PA, Powers J, Moser AB. X-linked adrenoleukodystrophy. In: Scriver CR, Sly WS, Childs B, Beaudet AL, Valle D, Kinzler KW, Vogelstein B, editors. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw Hill; 2001. p. 3257–301.

    Google Scholar 

  24. van Geel BM, Bezman L, Loes DJ, Moser HW, Raymond GV. Evolution of phenotypes in adult male patients with X-linked adrenoleukodystrophy. Ann Neurol. 2001;49(2):186–94.

    Article  PubMed  Google Scholar 

  25. Engelen M, Kemp S, de Visser M, van Geel BM, Wanders RJ, Aubourg P, et al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis. 2012;7:51. doi:10.1186/1750-1172-7-51. This review is especially useful to clinicians.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Dubey P, Raymond GV, Moser AB, Kharkar S, Bezman L, Moser HW. Adrenal insufficiency in asymptomatic adrenoleukodystrophy patients identified by very long-chain fatty acid screening. J Pediatr. 2005;146(4):528–32. doi:10.1016/j.jpeds.2004.10.067.

    Article  PubMed  Google Scholar 

  27. Assies J, Gooren LJ, Van Geel B, Barth PG. Signs of testicular insufficiency in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy: a retrospective study. Int J Androl. 1997;20(5):315–21.

    Article  PubMed  CAS  Google Scholar 

  28. van Geel BM, Koelman JH, Barth PG, de Visser Ongerboer BW. Peripheral nerve abnormalities in adrenomyeloneuropathy: a clinical and electrodiagnostic study. Neurology. 1996;46(1):112–8.

    Article  PubMed  Google Scholar 

  29. Horn MA, Nilsen KB, Jorum E, Mellgren SI, Tallaksen CM. Small nerve fiber involvement is frequent in X-linked adrenoleukodystrophy. Neurology. 2014;82(19):1678–83. doi:10.1212/WNL.0000000000000415.

    Article  PubMed  Google Scholar 

  30. Raymond GV, Seidman R, Monteith TS, Kolodny E, Sathe S, Mahmood A, et al. Head trauma can initiate the onset of adreno-leukodystrophy. J Neurol Sci. 2010;290(1–2):70–4. doi:10.1016/j.jns.2009.11.005.

    Article  PubMed  Google Scholar 

  31. Kemp S, Berger J, Aubourg P. X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta. 2012;1822(9):1465–74. doi:10.1016/j.bbadis.2012.03.012.

    Article  PubMed  CAS  Google Scholar 

  32. Van der Knaap MS, Valk J. X-linked adrenoleukodystrophy. In: Heilmann U, editor. Magnetic resonance of myelination and myelin disorders. Berlin: Springer; 2005. p. 176–90.

    Chapter  Google Scholar 

  33. Engelen M, Barbier M, Dijkstra IM, Schur R, de Bie RM, Verhamme C, et al. X-linked adrenoleukodystrophy in women: a cross-sectional cohort study. Brain. 2014;137(3):693–706. doi:10.1093/brain/awt361. This is a large prospective cohort study that systematically describes the phenotype of women with X-ALD.

    Article  PubMed  Google Scholar 

  34. El-Deiry SS, Naidu S, Blevins LS, Ladenson PW. Assessment of adrenal function in women heterozygous for adrenoleukodystrophy. J Clin Endocrinol Metab. 1997;82(3):856–60. doi:10.1210/jcem.82.3.3802.

    PubMed  CAS  Google Scholar 

  35. Jangouk P, Zackowski KM, Naidu S, Raymond GV. Adrenoleukodystrophy in female heterozygotes: underrecognized and undertreated. Mol Genet Metab. 2012;105(2):180–5. doi:10.1016/j.ymgme.2011.11.001.

    Article  PubMed  CAS  Google Scholar 

  36. Schaumburg HH, Powers JM, Raine CS, Suzuki K, Richardson Jr EP. Adrenoleukodystrophy. A clinical and pathological study of 17 cases. Arch Neurol. 1975;32(9):577–91.

    Article  PubMed  CAS  Google Scholar 

  37. Musolino PL, Rapalino O, Caruso P, Caviness VS, Eichler FS. Hypoperfusion predicts lesion progression in cerebral X-linked adrenoleukodystrophy. Brain. 2012;135(9):2676–83. doi:10.1093/brain/aws206.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Phillips JP, Lockman LA, Shapiro EG, Blazar BR, Loes DJ, Moser HW, et al. CSF findings in adrenoleukodystrophy: correlation between measures of cytokines, IgG production, and disease severity. Pediatr Neurol. 1994;10(4):289–94.

    Article  PubMed  CAS  Google Scholar 

  39. Schaumburg HH, Richardson EP, Johnson PC, Cohen RB, Powers JM, Raine CS. Schilder’s disease. Sex-linked recessive transmission with specific adrenal changes. Arch Neurol. 1972;27(5):458–60.

    Article  PubMed  CAS  Google Scholar 

  40. Hoftberger R, Kunze M, Weinhofer I, Aboul-Enein F, Voigtlander T, Oezen I, et al. Distribution and cellular localization of adrenoleukodystrophy protein in human tissues: implications for X-linked adrenoleukodystrophy. Neurobiol Dis. 2007;28(2):165–74. doi:10.1016/j.nbd.2007.07.007.

    Article  PubMed  Google Scholar 

  41. Moser HW, Moser AB, Frayer KK, Chen W, Schulman JD, O’Neill BP, et al. Adrenoleukodystrophy: increased plasma content of saturated very long chain fatty acids. Neurology. 1981;31(10):1241–9.

    Article  PubMed  CAS  Google Scholar 

  42. Singh I, Moser HW, Moser AB, Kishimoto Y. Adrenoleukodystrophy: impaired oxidation of long chain fatty acids in cultured skin fibroblasts an adrenal cortex. Biochem Biophys Res Commun. 1981;102(4):1223–9.

    Article  PubMed  CAS  Google Scholar 

  43. Singh I, Moser AE, Moser HW, Kishimoto Y. Adrenoleukodystrophy: impaired oxidation of very long chain fatty acids in white blood cells, cultured skin fibroblasts, and amniocytes. Pediatr Res. 1984;18(3):286–90. doi:10.1203/00006450-198403000-00016.

    Article  PubMed  CAS  Google Scholar 

  44. Kemp S, Valianpour F, Mooyer PA, Kulik W, Wanders RJ. Method for measurement of peroxisomal very-long-chain fatty acid beta-oxidation in human skin fibroblasts using stable-isotope-labeled tetracosanoic acid. Clin Chem. 2004;50(10):1824–6. doi:10.1373/clinchem.2004.038539.

    Article  PubMed  CAS  Google Scholar 

  45. Kemp S, Mooyer PA, Bolhuis PA, van Geel BM, Mandel JL, Barth PG, et al. ALDP expression in fibroblasts of patients with X-linked adrenoleukodystrophy. J Inherit Metab Dis. 1996;19(5):667–74.

    Article  PubMed  CAS  Google Scholar 

  46. Wiesinger C, Kunze M, Regelsberger G, Forss-Petter S, Berger J. Impaired very long-chain acyl-CoA beta-oxidation in human X-linked adrenoleukodystrophy fibroblasts is a direct consequence of ABCD1 transporter dysfunction. J Biol Chem. 2013;288(26):19269–79. doi:10.1074/jbc.M112.445445.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  47. 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;90(4):1233–6.

    PubMed  CAS  Google Scholar 

  48. Kishimoto Y, Moser HW, Kawamura N, Platt M, Pallante SL, Fenselau C. Adrenoleukodystrophy: evidence that abnormal very long chain fatty acids of brain cholesterol esters are of exogenous origin. Biochem Biophys Res Commun. 1980;96(1):69–76.

    Article  PubMed  CAS  Google Scholar 

  49. Kemp S, Valianpour F, Denis S, Ofman R, Sanders RJ, Mooyer P, et al. Elongation of very long-chain fatty acids is enhanced in X-linked adrenoleukodystrophy. Mol Genet Metab. 2005;84(2):144–51. doi:10.1016/j.ymgme.2004.09.015.

    Article  PubMed  CAS  Google Scholar 

  50. Ofman R, Dijkstra IM, van Roermund CW, Burger N, Turkenburg M, van Cruchten A, et al. The role of ELOVL1 in very long-chain fatty acid homeostasis and X-linked adrenoleukodystrophy. EMBO Mol Med. 2010;2(3):90–7. doi:10.1002/emmm.201000061.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  51. Engelen M, Schackmann MJ, Ofman R, Sanders RJ, Dijkstra IM, Houten SM, et al. Bezafibrate lowers very long-chain fatty acids in X-linked adrenoleukodystrophy fibroblasts by inhibiting fatty acid elongation. J Inherit Metab Dis. 2012;35(6):1137–45. doi:10.1007/s10545-012-9471-4.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  52. Engelen M, Tran L, Ofman R, Brennecke J, Moser AB, Dijkstra IM, et al. Bezafibrate for X-linked adrenoleukodystrophy. PLoS One. 2012;7(7):e41013. doi:10.1371/journal.pone.0041013.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  53. Kemp S, Theodoulou FL, Wanders RJ. Mammalian peroxisomal ABC transporters: from endogenous substrates to pathology and clinical significance. Br J Pharmacol. 2011;164(7):1753–66. doi:10.1111/j.1476-5381.2011.01435.x.

    Article  PubMed  PubMed Central  Google Scholar 

  54. 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. Investig Cell Pathol. 1980;3(4):353–76.

    CAS  Google Scholar 

  55. Powers JM, Moser HW, Moser AB, Ma CK, Elias SB, Norum RA. Pathologic findings in adrenoleukodystrophy heterozygotes. Arch Pathol Lab Med. 1987;111(2):151–3.

    PubMed  CAS  Google Scholar 

  56. Powers JM, DeCiero DP, Ito M, Moser AB, Moser HW. Adrenomyeloneuropathy: a neuropathologic review featuring its noninflammatory myelopathy. J Neuropathol Exp Neurol. 2000;59(2):89–102.

    PubMed  CAS  Google Scholar 

  57. Powers JM, DeCiero DP, Cox C, Richfield EK, Ito M, Moser AB, et al. The dorsal root ganglia in adrenomyeloneuropathy: neuronal atrophy and abnormal mitochondria. J Neuropathol Exp Neurol. 2001;60(5):493–501.

    PubMed  CAS  Google Scholar 

  58. Whitcomb RW, Linehan WM, Knazek RA. Effects of long-chain, saturated fatty acids on membrane microviscosity and adrenocorticotropin responsiveness of human adrenocortical cells in vitro. J Clin Investig. 1988;81(1):185–8. doi:10.1172/JCI113292.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  59. Hein S, Schonfeld P, Kahlert S, Reiser G. Toxic effects of X-linked adrenoleukodystrophy-associated, very long chain fatty acids on glial cells and neurons from rat hippocampus in culture. Hum Mol Genet. 2008;17(12):1750–61. doi:10.1093/hmg/ddn066.

    Article  PubMed  CAS  Google Scholar 

  60. Galino J, Ruiz M, Fourcade S, Schluter A, Lopez-Erauskin J, Guilera C, et al. Oxidative damage compromises energy metabolism in the axonal degeneration mouse model of X-adrenoleukodystrophy. Antioxid Redox Signal. 2011;15(8):2095–107. doi:10.1089/ars.2010.3877.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  61. Powers JM, Pei Z, Heinzer AK, Deering R, Moser AB, Moser HW, et al. Adreno-leukodystrophy: oxidative stress of mice and men. J Neuropathol Exp Neurol. 2005;64(12):1067–79.

    Article  PubMed  CAS  Google Scholar 

  62. Lopez-Erauskin J, Galino J, Bianchi P, Fourcade S, Andreu AL, Ferrer I, et al. Oxidative stress modulates mitochondrial failure and cyclophilin D function in X-linked adrenoleukodystrophy. Brain. 2012;135(12):3584–98. doi:10.1093/brain/aws292.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Fourcade S, Lopez-Erauskin J, Galino J, Duval C, Naudi A, Jove M, et al. Early oxidative damage underlying neurodegeneration in X-adrenoleukodystrophy. Hum Mol Genet. 2008;17(12):1762–73. doi:10.1093/hmg/ddn085.

    Article  PubMed  CAS  Google Scholar 

  64. Pujol A, Hindelang C, Callizot N, Bartsch U, Schachner M, Mandel JL. Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum Mol Genet. 2002;11(5):499–505.

    Article  PubMed  CAS  Google Scholar 

  65. Eichler FS, Ren JQ, Cossoy M, Rietsch AM, Nagpal S, Moser AB, et al. Is microglial apoptosis an early pathogenic change in cerebral X-linked adrenoleukodystrophy? Ann Neurol. 2008;63(6):729–42. doi:10.1002/ana.21391.

    Article  PubMed  Google Scholar 

  66. Lu JF, Lawler AM, Watkins PA, Powers JM, Moser AB, Moser HW, et al. A mouse model for X-linked adrenoleukodystrophy. Proc Natl Acad Sci U S A. 1997;94(17):9366–71.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  67. Forss-Petter S, Werner H, Berger J, Lassmann H, Molzer B, Schwab MH, et al. Targeted inactivation of the X-linked adrenoleukodystrophy gene in mice. J Neurosci Res. 1997;50(5):829–43.

    Article  PubMed  CAS  Google Scholar 

  68. Kobayashi T, Shinnoh N, Kondo A, Yamada T. Adrenoleukodystrophy protein-deficient mice represent abnormality of very long chain fatty acid metabolism. Biochem Biophys Res Commun. 1997;232(3):631–6. doi:10.1006/bbrc.1997.6340.

    Article  PubMed  CAS  Google Scholar 

  69. Pujol A, Ferrer I, Camps C, Metzger E, Hindelang C, Callizot N, et al. Functional overlap between ABCD1 (ALD) and ABCD2 (ALDR) transporters: a therapeutic target for X-adrenoleukodystrophy. Hum Mol Genet. 2004;13(23):2997–3006. doi:10.1093/hmg/ddh323.

    Article  PubMed  CAS  Google Scholar 

  70. Kemp S, Pujol A, Waterham HR, van Geel BM, Boehm CD, Raymond GV, et al. ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. Hum Mutat. 2001;18(6):499–515. doi:10.1002/humu.1227.

    Article  PubMed  CAS  Google Scholar 

  71. Asheuer M, Bieche I, Laurendeau I, Moser A, Hainque B, Vidaud M, et al. Decreased expression of ABCD4 and BG1 genes early in the pathogenesis of X-linked adrenoleukodystrophy. Hum Mol Genet. 2005;14(10):1293–303. doi:10.1093/hmg/ddi140.

    Article  PubMed  CAS  Google Scholar 

  72. Miller WP, Rothman SM, Nascene D, Kivisto T, DeFor TE, Ziegler RS, et al. Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 2011;118(7):1971–8. doi:10.1182/blood-2011-01-329235.

    Article  PubMed  CAS  Google Scholar 

  73. Loes DJ, Hite S, Moser H, Stillman AE, Shapiro E, Lockman L, et al. Adrenoleukodystrophy: a scoring method for brain MR observations. AJNR Am J Neuroradiol. 1994;15(9):1761–6.

    PubMed  CAS  Google Scholar 

  74. 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. 2009;326(5954):818–23. doi:10.1126/science.1171242.

    Article  PubMed  CAS  Google Scholar 

  75. Aubourg P, Adamsbaum C, Lavallard-Rousseau MC, Rocchiccioli F, Cartier N, Jambaque I, et al. A two-year trial of oleic and erucic acids (“Lorenzo’s oil”) as treatment for adrenomyeloneuropathy. N Engl J Med. 1993;329(11):745–52. doi:10.1056/NEJM199309093291101.

    Article  PubMed  CAS  Google Scholar 

  76. van Geel BM, Assies J, Haverkort EB, Koelman JH, Verbeeten Jr B, Wanders RJ, et al. Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with “Lorenzo’s oil”. J Neurol Neurosurg Psychiatry. 1999;67(3):290–9.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Horn MA, Erichsen MM, Wolff AS, Mansson JE, Husebye ES, Tallaksen CM, et al. Screening for X-linked adrenoleukodystrophy among adult men with Addison’s disease. Clin Endocrinol. 2013;79(3):316–20. doi:10.1111/cen.12159.

    Article  CAS  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Marc Engelen, Stephan Kemp and Bwee-Tien Poll-The declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Department of Pediatric Neurology/Emma Children’s Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, 1100 DD, The Netherlands

    Marc Engelen, Stephan Kemp & Bwee-Tien Poll-The

  2. Department of Pediatric Neurology, Academisch Medisch Centrum, Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands

    Marc Engelen, Stephan Kemp & Bwee-Tien Poll-The

Authors
  1. Marc Engelen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephan Kemp
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bwee-Tien Poll-The
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bwee-Tien Poll-The.

Additional information

This article is part of the Topical Collection on Demyelinating Disorders

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Engelen, M., Kemp, S. & Poll-The, BT. X-Linked Adrenoleukodystrophy: Pathogenesis and Treatment. Curr Neurol Neurosci Rep 14, 486 (2014). https://doi.org/10.1007/s11910-014-0486-0

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-014-0486-0

Keywords

Search

Navigation