X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): an update

Am J Med Genet A. 2004 May 1;126A(4):349-54. doi: 10.1002/ajmg.a.20660.


X-linked cardioskeletal myopathy and neutropenia (Barth syndrome, MIM302060, BTHS) is a disorder with mitochondrial functional impairments and 3-methylglutaconic aciduria that maps to Xq28. The associated G4.5 or TAZ gene has been identified but the encoded proteins have not yet been characterized. Following the prediction that the gene encodes one or more acyltransferases, lipid studies have shown a deficiency of cardiolipin, especially its tetralinoleoyl form (L(4)-CL). Deficiency of L(4)-CL was subsequently demonstrated in a variety of tissues, and determination in thrombocytes or cultured skin fibroblasts is now the most specific biochemical test available. BTHS is the first identified inborn error of metabolism that directly affects cardiolipin, a component of the inner mitochondrial membrane, necessary for proper functioning of the electron transport chain. We report here the finding of deficient docosahexaenoic acid and arachidonic acid in a proportion of patients with BTHS. The initial impression of a uniformly lethal infantile disease has to be modified. Age distribution in 54 living patients ranges between 0 and 49 years and peaks around puberty. Mortality is the highest in the first 4 years. The apex of the survival curve around puberty and the emergence of adults may reflect a dynamic shift towards increased survival. This trend is exemplified in a large pedigree previously published.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / mortality
  • Abnormalities, Multiple / pathology*
  • Cardiolipins / analysis
  • Cardiomyopathy, Dilated / pathology
  • Female
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / metabolism
  • Genetic Diseases, X-Linked / pathology*
  • Humans
  • Lipids / blood
  • Male
  • Muscular Diseases / pathology
  • Mutation
  • Neutropenia / pathology
  • Pedigree
  • Proteins / genetics
  • Survival Rate
  • Syndrome
  • Transcription Factors / genetics


  • Cardiolipins
  • Lipids
  • Proteins
  • TAZ protein, human
  • Transcription Factors