Barth syndrome (BTHS) is a multisystem disorder of individuals who carry mutations in tafazzin, a putative phospholipid acyltransferase. BTHS is probably caused by specific impairment of the mitochondrial lipid metabolism.

Synopsis

 cardiac anomalies

• dilated cardiomyopathy with cardiac failure
• endocardial fibroelastosis

 hematological anomalies

• neutropenia (granulocytopenia) *- agranulocytosis

 sepsis

• pseudomembranous pharyngitis
• postinflammatorial pharyngeal stenosis (#12623146#)

 skeletal myopathy
 growth retardation

Laboratory invetsigations

 Persistently elevated urinary levels of 3-methylglutaconate, 3-methylglutarate, and 2-ethylhydracrylate.
 The fatty acid composition of all major mitochondrial phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL), changed in lymphoblasts from BTHS patients. (#15806137#)

• most extensive in CL
• least extensive in PE
• The complementary nature of the fatty acid alterations in CL and PC suggested that fatty acid transfer between these two lipids was inhibited in BTHS.

 Fluorescence staining and electron microscopy showed abnormal proliferation of mitochondria in BTHS lymphoblasts. (#15806137#)

• The mitochondrial membrane potential, monitored with the fluorescence probe JC-1, was reduced in BTHS lymphoblasts.
• Mitochondrial ATP formation of permeabilized lymphoblasts remained unaffected in BTHS.

 Phospholipid abnormalities of BTHS mitochondria led to partial uncoupling of oxidative phosphorylation and that lymphoblasts compensated for this deficiency by expanding the mitochondrial compartment. (#15806137#)

Ultrastructure

 abnormal mitochondria in cardiomyocytes and granulocyte precursors

• concentric, tightly packed cristae
• occasional inclusion bodies
• increased numbers of mitochondria
• abnormal mitochondrial crystal condensations
• paracrystalline inclusions

Etiology

 Barth syndrome is caused by mutation in the tafazzin gene (TAZ) (MIM.300394)

References

 Huhta JC, Pomerance HH, Barness EG. Clinicopathologic conference: barth syndrome. Fetal Pediatr Pathol. 2005 Jul-Aug;24(4):239-54. PMID: #16396830#

 Xu Y, Sutachan JJ, Plesken H, Kelley RI, Schlame M. Characterization of lymphoblast mitochondria from patients with Barth syndrome. Lab Invest. 2005 Apr 4 PMID: #15806137#

 Barth PG, Valianpour F, Bowen VM, Lam J, Duran M, Vaz FM, Wanders RJ. X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): an update. Am J Med Genet A. 2004 May 1;126(4):349-54. PMID: #15098233#