Barth syndrome is a very rare genetic disorder, which only affects males. The most serious problems in Barth syndrome are heart muscle weakness (see entry, Cardiomyopathy) and increased susceptibility to bacterial infections. This susceptibility is caused by a reduction in the number of certain white blood cells, called neutrophils. Neutrophil numbers often vary with time in this condition and patients are said to have 'cyclical neutropenia.' Other features include short stature and muscle weakness, which can lead to fatigue or delayed motor development in early childhood. Analysis of urine usually shows increased quantities of certain organic acids (3-methylglutaconic and, sometimes, 2-ethylhydracrylic).

The features of Barth syndrome vary between different families and even within the same family, but the majority of patients develop cardiomyopathy within the first year. Typical early features are laboured breathing and poor feeding due to breathlessness ('heart failure'). Often the heart failure can be controlled by drug treatment but, in a few patients, heart transplantation may need to be considered. A few patients die suddenly, before they are diagnosed, perhaps due to a disturbance of the heart's rhythm. Other patients may die because of overwhelming infections.

Barth syndrome is caused by mutations in a gene called G4.5. This gene is located on the X chromosome (Xq28). Ultimately, the genetic abnormality impairs the ability of cells to produce energy. At the cellular level, the problem is mediated by abnormalities in a protein called a tafazzin and by decreased production of a fat called cardiolipin.

There is no specific treatment for Barth syndrome but many patients have a good outcome, with treatment for heart failure and appropriate use of antibiotics. The cardiomyopathy and susceptibility to infections both tend to improve as patients grow older.

Inheritance patterns
Barth syndrome is inherited as an X-linked recessive trait. Because males only have one X chromosome, they only have one copy of the G4.5 gene and they run into problems if this is faulty. In contrast, females have two X chromosomes: if they have a faulty copy of G4.5, they are asymptomatic because they still have one normal copy. A carrier female can, however, pass the faulty gene on to her children: her sons have a fifty per cent chance of being affected and her daughters have a fifty per cent chance of being carriers. Detailed genetic counselling is advisable when Barth syndrome is identified in a family.

Prenatal diagnosis
Prenatal diagnosis is possible at an early stage in pregnancy in families where the mutation is known. Suitable specimens can be obtained by amniocentesis or chorionic villus sampling.

Medical text written October 2003 by Contact a Family. Approved October 2003 by Dr A Morris, Consultant Paediatrician with Special Interest In Metabolic Disease, Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, UK.

Barth Syndrome Trust
c/o Contact a Family
209-211 City Road
London
EC1V 1JN
Tel: 01794 518785
Fax: 0870 706 6360
e-mail: info@barthsyndrome.org.uk
Web: http://www.barthsyndrome.org.uk

The Trust is a National Registered Charity No. 1100835, established in 2003 to provide information and support families.. It aims to raise awareness about Barth syndrome amongst health professionals and to raise funds to support research. Health professionals are welcome to contact the Trust for information. The Trust maintains strong links with world-class experts involved in treating this disorder. It also works closely with affiliated support groups around the world.

Group details last confirmed June 2007.