Barth syndrome: clinical observations and genetic linkage studies

Barth syndrome is an X-linked recessive condition characterized by skeletal myopathy, cardiomyopathy, proportionate short stature, and recurrent neutropenia, but with normal cognitive function. Some, but not all patients, exhibit carnitine deficiency and/or the presence of 3-methylglutaconic and ethylhydracylic acids in urine. Recently the mutation causing Barth syndrome was localised to the Xq28 region by linkage analysis. We report 6 cases of Barth syndrome from 4 families and highlight the fact that neuromuscular and cardiovascular symptoms and the severity of infections tend to improve with age, while short stature persists. Also previously unreported was myopathic facies and nasal quality to speech in our cases. The urinary organic acid abnormalities and plasma carnitine deficiency were inconsistent findings. We propose that they may be epiphenomena rather than indicators of the primary metabolic defect, and that the primary defect or defects in this disorder may lie in the mitochondrial electron transport chain.