Any of their children might inherit the modified gene with a 50% probability, with the males developing Barth Syndrome and the females going on to be carriers themselves. Thus, it is vitally important to take familial histories of Barth Syndrome patients in order to determine genetic risk. Ideally, any male who is matrilineally related to an individual with Barth Syndrome should be tested for TAZ mutation(s). Because the phenotype can vary widely, even among affected siblings, symptomatology (or lack thereof) by itself is insufficient for diagnosis. Diagnosis
Early diagnosis of the syndrome is complicated, but of critical importance. Clinical presentation in Barth Syndrome is highly variable, with the only common denominator being early-onset and pronounced cardiomyopathy. Diagnosis is established based upon several tests, among which can be blood tests (neutropenia, white blood cell count), urinalysis (increased urinary organic acid levels), echocardiography (cardiac ultrasound, to assess (and detect abnormalities in) the hearts structure, function and condition), and, with reasonable suspicion of Barth Syndrome, DNA sequencing (to verify TAZ gene status). Differential diagnosis
Based on symptoms at time of presentation, the differential diagnosis may include other hereditary and/or nutritional causes of (dilated) cardiomyopathy and (cyclic or idiopathic) neutropenia. Treatment
Currently, there is no treatment for Barth syndrome, although some of the symptoms can be successfully managed. Clinical trials for possible treatments are ongoing, and preliminary research into AAV9-mediated TAZ gene replacement by the University of Florida has been promising.
However, more research and (pre-)clinical testing is needed before the gene therapy is eligible for approval by the FDA as a treatment modality. Epidemiology
Being X-linked, Barth syndrome has been predominantly diagnosed in males (as of July 2009: 120+ males), although by 2012 a female case had been reported.The syndrome is believed to be severely under-reported due to the complexity of (early) diagnosis. Reports on its incidence and prevalence in the international literature vary; around 1 in every 454,000 individuals are thought to suffer from Barth Syndrome. Incidence has been estimated at anywhere between 1:140,000 (South West England, South Wales) and 1:300,000 - 1:400,000 live births (United States). Geographical distribution is homogenous, with patients (and their family members) on every continent (with known cases in, for example, the US, Canada, Europe, Japan, South Africa, Kuwait, and Australia). History
The syndrome was named for Dr. Peter Barth (b. 1932), a Dutch pediatric neurologist, for his research into and the discovery of the syndrome in 1983. He described a pedigree chart, showing that this is an inherited trait and not a communicated (i.e. infectious) disease. See also
3-Methylglutaconic aciduria
noncompaction cardiomyopathy: mutations to the affected genes in Barth syndrome are also present here. References
External links
Barth Syndrome at NINDS