OBJECTIVE: Barth syndrome, an X-linked disorder that is characterized by 
cardiomyopathy, neutropenia, skeletal myopathy, and growth delay, is caused by 
mutations in the taffazin gene at Xq28 that result in cardiolipin deficiency and 
abnormal mitochondria. The clinical phenotype in Barth syndrome has not been 
characterized systematically, and the condition may be underrecognized. We 
sought to evaluate extent of cardioskeletal myopathy, potential for arrhythmia, 
delays in growth, and biochemical correlates of disease severity in patients 
with this disorder.
METHODS: We conducted an observational, cross-sectional study of the largest 
cohort of patients with Barth syndrome to date (n = 34; age range: 1.2-22.6 
years). Evaluation included echocardiography, electrocardiography (standard and 
signal-averaged), microvolt T wave alternans analysis, biochemical and 
hematologic laboratory analyses, and physical therapy evaluation of skeletal 
myopathy.
RESULTS: Family history was positive for confirmed or suspected Barth syndrome 
in 63%. Ninety percent of patients had a clinical history of cardiomyopathy 
(mean age at diagnosis of cardiomyopathy: 5.5 months; at genetic confirmation of 
Barth syndrome: 4.6 years). Echocardiography revealed a mean ejection fraction 
of 50% +/- 10%, mean fractional shortening of 28% +/- 5%, and mean left 
ventricular end-diastolic volume z score of 1.9 +/- 1.8. Left ventricular 
morphology demonstrated increased trabeculations or true noncompaction in 53%. 
Of 16 patients who were evaluated at > or = 11 years of age, 7 (43%) had 
documented ventricular arrhythmia. Growth deficiency was present (mean weight 
percentile: 15%; mean height percentile: 8%). Laboratory analysis revealed low 
total white blood cell count (absolute count: < 4000 cells per microL) in 25% of 
those who were not on granulocyte colony-stimulating factor. Hypocholesterolemia 
was present in 24%, decreased low-density lipoprotein cholesterol in 56%, low 
prealbumin in 79%, and mildly elevated creatine kinase in 15%.
CONCLUSIONS: Our cohort demonstrated clinical variability, but most had 
cardiomyopathy and diminished growth velocity, with a propensity toward 
neutropenia and low cholesterol. There was increased incidence of ventricular 
arrhythmia, predominantly in adolescents and young adults. Barth syndrome should 
be considered when boys present with cardiomyopathy, especially when associated 
with increased left ventricular trabeculations, neutropenia, skeletal muscle 
weakness, or family history indicating an X-linked pattern of inheritance.