X-linked cardioskeletal myopathy, neutropenia and abnormal mitochondria (MIM 
302060) (synonyms: Barth syndrome, 3-methylglutaconic acid-uria type II, 
endocardial fibroelastosis type 2) has been reported in patients and families 
from Europe, North America and Australia. Previous studies characterized the 
main components of the disease: dilated cardiomyopathy, skeletal myopathy, 
neutropenia, 3-methylglutaconic aciduria and diminished statural growth. 
Respiratory chain impairments have been found in several studies, without 
pinpointing a single enzyme complex. 3-Methylglutaconic aciduria is shared with 
several other disorders that affect the respiratory chain. Previous studies 
excluded a block in the major pathway of leucine catabolism. We performed 
leucine loading, accompanied by fasting, in patients and observed a significant 
rise of 3-methylglutaconic acid and 3-methylglutaric acid. Taken together with 
the absence of an enzymatic block in the major leucine catabolic route, the 
possibility remains that the increased basal excretion of 3-methylglutaconic 
acid and other products of branched-chain amino acids is the result of overload 
of this pathway or--more likely--mitochondrial leakage. Linkage studies have 
localized the gene to the Xq28 region. The associated tafazzin gene (TAZ), has 
been fully characterized recently, and mutations located in conserved regions 
have been reported. Carrier detection and prenatal diagnosis have now become 
possible through mutation analysis. Sequence homology of the TAZ gene to a 
highly conserved superclass of acyltransferases (Neuwald's hypothesis) predicts 
a glycerophospholipid as the missing end product. This points to the (lipid) 
structure of the inner mitochondrial membrane as a promising new area of 
research.