Phospholipid abnormalities in children with Barth syndrome

Area of Science:

• Biochemistry
• Genetics
• Cardiology

Background:

• Barth syndrome (BTHS) presents with cardiomyopathy, myopathy, neutropenia, growth retardation, and 3-methylglutaconic aciduria.
• Mutations in the tafazzin (TAZ) gene are common in BTHS, but similar features occur in patients with normal TAZ.
• TAZ gene products are homologous to phospholipid acyltransferases, suggesting a role in lipid metabolism.

Purpose of the Study:

• Identify characteristic lipid abnormalities in BTHS patients.
• Correlate lipid profiles with BTHS phenotype and genotype.
• Determine if lipid abnormalities are specific to BTHS caused by TAZ mutations.

Main Methods:

• Analyzed phospholipid molecular species in various tissues (heart, muscle, platelets, lymphoblasts, fibroblasts).
• Studied 19 children with BTHS (TAZ mutation), 6 with BTHS-like syndromes (wild-type TAZ), and 4 with isolated cardiomyopathy.
• Compared lipid profiles against control groups.

Main Results:

• Cardiolipin, a mitochondrial lipid, was decreased in all tissues of BTHS patients.
• The molecular composition of cardiolipin was altered in all BTHS tissues; phosphatidylcholine and phosphatidylethanolamine were altered in the heart.
• Cardiolipin abnormalities were specific to true BTHS, absent in BTHS-like or isolated cardiomyopathy cases.
• Cardiolipin deficiency was tissue-specific but did not correlate with disease severity or phenotype.

Conclusions:

• Abnormal cardiolipin is a specific diagnostic marker for cardiomyopathies resulting from TAZ mutations.
• TAZ mutations alter the fatty acid composition of phospholipids, supporting TAZ's role as a human acyltransferase.
• This study highlights the utility of lipid analysis in diagnosing genetic disorders like BTHS.