Metabolic Brain Disease

, Volume 23, Issue 1, pp 43–49 | Cite as

Hexacosanoic and docosanoic acids plasma levels in patients with cerebral childhood and asymptomatic X-linked adrenoleukodystrophy: Lorenzo’s oil effect

  • Marion Deon
  • Mariana Pires Garcia
  • Angela Sitta
  • Alethéa G. Barschak
  • Daniella M. Coelho
  • Graziela O. Schimit
  • Maiara Pigatto
  • Laura B. Jardim
  • Moacir Wajner
  • Roberto Giugliani
  • Carmen R. Vargas
Original Paper

Abstract

X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal metabolism, biochemically characterized by deficient β-oxidation of saturated very long chain fatty acids (VLCFA). The consequent accumulation of these fatty acids in different tissues and in biological fluids is associated with a progressive central and peripheral demyelination, as well as with adrenocortical insufficiency and hypogonadism. Seven variants of this disease have been described, being cerebral childhood the most frequent. The recommended therapy consists of the use of the glyceroltrioleate/glyceroltrierucate mixture known as Lorenzo’s Oil (LO), combined with a VLCFA-poor diet, but only in asymptomatic patients will this treatment prevent the progression of the symptomatology. In the present study we evaluated the biochemical course of patients with cerebral childhood (CCER) and asymptomatic clinical forms of X-ALD treated with LO associated with a VLCFA-restricted diet. We observed that hexacosanoic acid plasma concentrations and hexacosanoic/docosanoic ratio were significantly reduced in CCER patients during treatment when compared with diagnosis. Hexacosanoic acid plasma level was significantly reduced when compared with that at diagnosis and achieved the normal levels only in asymptomatic patients under LO treatment. In asymptomatic patients the magnitude of hexacosanoic acid decrease was higher than that of the CCER patients. These results show the good biochemical response of LO treatment in asymptomatic X-ALD patients. It is possible to suppose that this could be correlated with the prevention of the appearance of neurological signals in this group of patients treated with LO.

Keywords

Adrenoleukodystrophy Hexacosanoic acid Tetracosanoic acid Lorenzo’s Oil Peroxisomes Very long chain fatty acids 

Notes

Acknowledgment

This research was supported by grants from CAPES, CNPq, FAPERGS, PROPESQ/UFRGS and FIPE/HCPA.

References

  1. Altman DG (1991) Practical Statistics for Medical Research. Chapman & Hall, LondonGoogle Scholar
  2. Dubey P, Raymond GV, Moser AB, Kharkar S, Bezman L, Moser HW (2005) Adrenal insufficiency in asymptomatic adrenoleucodystrophy patients identified by very long chain fatty acid screening. J Pediatr 146(4):528–32PubMedCrossRefGoogle Scholar
  3. Korenke GC, Hunneman DH, Kohler J, Stöckler S, Landmark K, Hanefeld F (1995) Glyceroltrioleato/glyceroltrierucate therapy in 16 patients with X-chromosomal adrenoleukodystrophy/adrenomyeloneuropathy: effect on clinical, biochemical and neurophysiological parameters. Eur J Pediatr 154:64–70PubMedCrossRefGoogle Scholar
  4. Mahmood A, Dubey P, Moser HW, Moser A (2005) X-linked adrenoleukodystrophy: therapeutic approaches to distinct phenotypes. Pediatr Transplantation 9(7):55–62CrossRefGoogle Scholar
  5. Moser HW (1997) Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain 120:1485–1508PubMedCrossRefGoogle Scholar
  6. Moser HW (2006) Therapy of X-linked Adrenoleukodystrophy. NeuroRx 3:246–253PubMedCrossRefGoogle Scholar
  7. Moser HW, Moser AB (1991) Measurement of saturated very long chain fatty acid in plasma. In: Hommes FA (ed) Techniques of diagnostic human biochemical genetics. Wiley, New YorkGoogle Scholar
  8. Moser HW, Smith KD, Watkins PA, Powers J, Moser AB (2001) X-linked adrenoleukodystrophy. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. 8th edn. McGraw-Hill, New YorkGoogle Scholar
  9. Moser HW, Dubey P, Fatemi A (2004) Progress in X-linked adrenoleukodystrophy. Curr Opin Neurol 17:263–269PubMedCrossRefGoogle Scholar
  10. Moser HW, Raymond GV, Lu SE, Muenz LR, Moser AB, Xu J, Jones RO, Loes DJ, Melhem ER, Dubey P, Bezman L, Brereton NH, Odone A (2005) Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo’s oil. Arch Neurol 62(7):1073–80PubMedCrossRefGoogle Scholar
  11. Restuccia D, Di Lazzaro V, Valeriani M, Oliviero A, Le Pera D, Barba C, Cppa M, Bertini E, Di Capua M, Tonali P (1999) Neurophysiologic follow-up of long-term dietary treatment in adult-onset adrenoleukodystrophy. Neurology 52:810–815PubMedGoogle Scholar
  12. Ruiz M, Pampols T, Girós M (1996) Glycerol trioleato/glycerol trierucate therapy in X-linked adrenoleukodystrophy: Saturated and unsaturated fatty acids in blood cells. Implications for the follow-up. J Inher Metab Dis 19:188–192PubMedCrossRefGoogle Scholar
  13. Suzuki Y, Imamura A, Shimozawa N, Kondo N (2001) The clinical course of childhood and adolescent adrenoleukodystrophy before and after Lorenzo’s oil. Brain Dev 23(1):30–3PubMedCrossRefGoogle Scholar
  14. van Geel BM, Assies J, Wanders RJA, Barth PG (1997) X-linked adrenoleukodystrophy: clinical, presentation, diagnosis and therapy. J Neurol Neurosurg Psychiatry 63:4–14PubMedCrossRefGoogle Scholar
  15. van Geel BM, Assies J, Haverkort EB, Koelman JHTM, Verbeeten B Jr, Wander RJA, Barth PG (1999) Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with Lorenzo’s oil. J Neurol Neurosurg Psychiatr 67(3):290–299PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Marion Deon
    • 3
  • Mariana Pires Garcia
    • 1
  • Angela Sitta
    • 3
  • Alethéa G. Barschak
    • 3
  • Daniella M. Coelho
    • 2
  • Graziela O. Schimit
    • 2
  • Maiara Pigatto
    • 1
  • Laura B. Jardim
    • 2
  • Moacir Wajner
    • 2
    • 3
  • Roberto Giugliani
    • 2
    • 3
  • Carmen R. Vargas
    • 1
    • 2
    • 3
    • 4
  1. 1.Departamento de Análises Clínicas, Faculdade de FarmáciaUFRGSPorto AlegreBrasil
  2. 2.Serviço de Genética MédicaHCPAPorto AlegreBrasil
  3. 3.Departamento de Bioquímica, ICBSUFRGSPorto AlegreBrasil
  4. 4.Medical Genetics ServiceHCPAPorto AlegreBrazil

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