Barth syndrome


3-Methylglutaconic aciduria type II


Barth syndrome (BTHS, also known as 3-Methylglutaconic aciduria type II), is an X-linked genetic disorder. The disorder, which affects multiple body systems, is diagnosed almost exclusively in males. It is named after Dutch pediatric neurologist Peter Barth.


This medical information about signs and symptoms for Barth Syndrome has been gathered from various sources, may not be fully accurate, and may not be the full list of Barth Syndrome signs or symptoms. Furthermore, signs and symptoms of Barth Syndrome may vary on an individual basis for each patient. Only your doctor can provide adequate diagnosis of any signs or symptoms and whether they are indeed Barth Syndrome symptoms.

The list of signs and symptoms mentioned in various sources for Barth Syndrome includes the 10 symptoms listed below:  

  • Skeletal myopathy 
  • Neutropenia
  • Growth retardation 
  • Endocardial fibroelastosis 
  • Weak heart 
  • Enlarged heart 
  • Low level of white blood cells 
  • Skeletal problems 
  • Delayed growth 
  • Increased urine level of 3-methylglutaconic acid 
  • Increased urine level of 2-ethyl-hydracrilic acid


Mutations in the tafazzin gene (TAZ, also called G4.5) are closely associated with Barth syndrome. The tafazzin gene product is believed to function as an acyltransferase in complex lipid metabolism. In 2008, Dr. Kulik found that all the BTHS individuals that he tested had abnormalities in their cardiolipin molecules, a lipid found inside the mitochondria of cells. Cardiolipin is intimately connected with the electron transport chain proteins and the membrane structure of the mitochondria which is the energy producing organelle of the cell. The human tafazzin gene, NG_009634, is listed as over 10,000 base pairs in length and the full-length mRNA, NM_000116, is 1919 nucleotides long encoding 11 exons with a predicted protein length of 292 amino acids and a molecular weight of 33.5 kDa. The tafazzin gene is located at Xq28; the long arm of the X chromosome. Mutations in tafazzin that cause Barth syndrome span many different categories: missense, nonsense, deletion, frameshift, splicing (see Human Tafazzin (TAZ) Gene Mutation & Variation Database).

iPLA2-VIA has been suggested as a target for treatment.


Diagnosis was historically based on metabolic screening of urine showing elevated excretion of organic acids (typically 3-methylglutaconic acid (3-MGCA)), followed by TAZ gene sequencing. However, 3-MGC excretion may be normal even in severe cases. Analysis of the ratio of monolysocardiolipin (MLCL) / cardiolipin (CL) on blood, tissue, fibroblasts or stored neonatal bloodspots is therefore the diagnostic test of choice.

Differential diagnosis includes hereditary, dilated and nutritional cardiomyopathy and idiopathic/cyclic neutropenia (see these terms).

Prenatal diagnosis (chorionic villus biopsy and/or amniocentesis) is possible in families in which the mutation is known.


Prognosis has greatly improved with early detection and improvements in treatment and management. Patients are already surviving into their 40s and are expected to live beyond this age.