Name of Condition
Barth syndrome (BTHS; OMIM #302060)
Barth syndrome is a rare but serious genetic disorder primarily affecting males around the world. It is caused by a mutation in the tafazzin gene (TAZ, also called G4.5), resulting in an inborn error of lipid metabolism.
Description, Signs and Symptoms
Though not always present, cardinal characteristics of this multi-system disorder often include combinations and varying degrees of:
- Cardiomyopathy (Dilated with variable myocardial hypertrophy, sometimes with left ventricular noncompaction and/or endocardial fibroelastosis)
- Neutropenia (Chronic, cyclic, or intermittent)
- Underdeveloped skeletal musculature and muscle weakness
- Growth delay (Abnormal growth pattern, similar to but often more severe than constitutional growth delay)
- Exercise intolerance
- Cardiolipin abnormalities
- 3-Methylglutaconic Aciduria, Type II (MGA, Type II) (Typically 5 to 100-fold increased)
Important Clinical Problems May Include (in varying severity):
- Congestive heart failure
- Life-threatening bacterial infection
- Gross motor delay
- Risk of fatal arrhythmia
- Short stature in the early years, followed by accelerated growth in late puberty
- Extreme fatigue
- Diarrhea and/or constipation
- Recurrent mouth ulcers
- Feeding problems
- Risk of thrombosis
- Diminished capacity for exercise
- Hypoglycemia, including fasting hypoglycemia (especially in the newborn period)
- Chronic headache, abdominal pain, and/or body aches (especially during puberty)
- Some mild learning disabilities
Barth syndrome (BTHS) is an X-linked genetic condition, usually transmitted from mother to son (though there is a relatively high incidence of new mutations in BTHS). A mother who is a carrier of a Barth syndrome mutation (the gene is named tafazzin —also called TAZ or G4.5) shows no signs or symptoms of this disorder herself, which is probably related to skewed X-chromosome inactivation.
There is a 50% chance that a boy born to a female carrier will have BTHS, whereas girls born to a carrier have a 50% risk of being carriers themselves. All daughters of a male with BTHS will be carriers; however, none of his sons will be affected. Because there are some proven non-carrier mothers, it is recommended that all mothers of BTHS children be tested in order to define the genetic risk in each family.
Any male child in a family with one BTHS individual should be tested for the disease, as there can be great variation in phenotype even among affected siblings.
To date, the Barth Syndrome Foundation  is aware of 117 living Barth syndrome individuals worldwide, but there is evidence that it is underdiagnosed.
Barth syndrome (BTHS) is a complex, multi-system disorder. It can be difficult to recognize because all manifestations may not be simultaneously present or apparent.
The diagnosis of BTHS should be considered for a child or adult presenting with any one of its seven cardinal characteristics or in cases with family histories of multiple male deaths or fetal loss.
- DNA sequence analysis (genetic testing) of the tafazzin gene (TAZ, also called G4.5)
- Cardiolipin analysis of various cells and tissues
Lack of family history does not exclude the diagnosis of BTHS, as there is a relatively high frequency of new mutations.
Treatment and Management
There is no specific treatment for Barth syndrome (BTHS). Bacterial infections caused by neutropenia can be effectively treated with antibiotics. The drug granulocyte colony stimulating factor, or GCSF, can stimulate white cell production by the bone marrow and help combat infection. Medicines may be prescribed to control heart problems. The dietary supplement carnitine has aided some Barth children, but in others it has caused increasing muscle weakness and even precipitated heart failure. Only careful dietary monitoring directed by a physician or nutritionist familiar with the disorder can ensure proper caloric and nutritional intake.
Early and accurate diagnosis is key to prolonged survival for boys born with Barth syndrome. Severe infections and cardiac failure are common causes of death in affected children.
AccessDNA.com - 3-Methylglutaconic Aciduria