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Barth syndrome

Friday 22 October 2004

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

- 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