Diagnosis of Barth Syndrome

Barth syndrome (BTHS): OMIM (#302060)

Alternative Descriptions
Noncompaction of the left ventricular myocardium, Familial isolated, X-linked; LVNCX or Cardiomyopathy, dilated, 3A; CMD3A

Gene Symbol
TAFAZZIN; TAZ

Alternative Symbol
G4.5

Gene Locus
Xq28; which falls on the long q arm of the X chromosome

Classification
Inborn Error in Metabolism

ICD 10 Code
Currently there is not an ICD 10 code specific for Barth syndrome; however, the Society for the Study of Inborn Errors in Metabolism (SSIEM) recommends E723.

Genotype/Phenotype Severity
To date there is no data supporting a genotype/phenotype relationship to predict the severity of the disorder.

Modifying Genes/Genetic Factors
Unknown, though variable phenotype would suggest modifying genes or influencing factors.

Inheritance
X-linked recessive

Ethnic Incidence
No known population at increased risk.

Prenatal Testing
Possible in cases of known mutation in family.

Newborn Screening
Though Tandem Mass Spectrometry (TMS) technology has made it possible to expand mass newborn screening, there are currently no reliable methods available for Barth syndrome.

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Symptom Onset
Varies, but generally within first year of life.

Natural History
Appropriate diagnosis renders the clinician with a better appreciation of the complex, multi-system involvement of the disorder. Though early diagnosis does not eliminate risk of morbidity and mortality, improved treatment strategies delivered with informed approach can improve outcomes.

Synonyms

1. Cardioskeletal Myopathy, Barth Type
2. Cardioskeletal Myopathy with Neutropenia and Abnormal Mitochondria
3. Endocardial Fibroelastosis, Type 2 (EFE2)
4. 3-Methylglutaconic Aciduria, Type II (MGA, Type II)
5. X-Linked Cardioskeletal Myopathy and Neutropenia

Abstract:

Barth syndrome is a rare, sex-linked genetic disorder of lipid metabolism that primarily affects males. Typically, boys with Barth syndrome present with hypotonia (low muscle tone) and dilated cardiomyopathy (labored breathing, poor appetite, and/or slow weight gain) at or within the first few months after birth. Other important features of Barth syndrome include bacterial infections because of neutropenia (a reduction in the number of white blood cells called neutrophils), muscle weakness, fatigue, and growth delay. Although most children with Barth syndrome manifest all of these characteristics, some have only one or two of these abnormalities and, as a result, often are given incorrect diagnoses.

Barth syndrome occurs in many different ethnic groups and does not appear to be more common in any one group. To date, there are no good studies of the population or birth incidence of Barth syndrome; however probably fewer than 10 new Barth infants are identified each year in the United States, which suggests an incidence of only 1 in every 300,000 – 400,000 births. The gene for Barth syndrome, Tafazzin (TAZ), is located on the long arm of the X chromosome (Xq28). Mutations in the TAZ gene lead to decreased production of an enzyme required for the synthesis of “cardiolipin,” a special lipid that is important in energy metabolism. There is no specific treatment for Barth syndrome, but each of the individual problems can be successfully controlled, and short stature often resolves after puberty.

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