X-linked adrenoleukodystrophy: clinical course and minimal incidence in South Brazil

Brain Dev. 2010 Mar;32(3):180-90. doi: 10.1016/j.braindev.2009.02.002. Epub 2009 Mar 6.

Abstract

X-linked adenoleukodystrophy is a genetic disease that affects the degradation of very long-chain fatty acids. In male patients, common pictures are the cerebral form (CALD), myeloneuropathy (AMN), and Addison-only.

Objective: To describe the clinical course of affected male patients from South Brazil between 1993 and 2007.

Methods: Affected male patients and their maternal lineages were studied from a clinical, neurological and biochemical standpoint.

Results: Eighty-three male patients from 30 families were biochemically evaluated: 51 were affected. 27/51 (54%) presented the cerebral form; 11/51 had AMN (22%); 5 had Addison-only (10%), and 8 (16%) were asymptomatic. Between 2002 and 2006, the minimal incidence was 1:35,000 males in our State (South Brazil). Forty-three affected individuals were followed for 5.4+/-3.7 years. Of 10 boys detected at early stages, three developed CALD. These three boys and another five CALD at baseline were referred to hematopoietic stem cell transplantation. Seven transplants were carried out, 5 with good clinical evolution after 2.2 years post-transplant. The non-transplanted case was later defined as a stable cerebral form.

Discussion: Among the present families, the observed cases were comparable to the 50% expected by Mendelian segregation. Based on the natural history, the number of cases that developed CALD was similar to the expected. Transplants were successful in 70% of cases. The occurrence of a stable cerebral form pointed to an urgent need for better markers of active cerebral disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenoleukodystrophy / epidemiology
  • Adrenoleukodystrophy / genetics*
  • Adrenoleukodystrophy / metabolism
  • Adrenoleukodystrophy / surgery*
  • Brazil / epidemiology
  • Chromatography, Gas / methods
  • Chromosomes, Human, X*
  • Coenzyme A Ligases / metabolism
  • Disease Progression
  • Family Health
  • Fatty Acids / metabolism
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Longitudinal Studies
  • Male
  • Retrospective Studies
  • Severity of Illness Index
  • Statistics, Nonparametric

Substances

  • Fatty Acids
  • hexacosanoic acid
  • Coenzyme A Ligases
  • behenic acid