Mutated gene: Barth syndrome occurs when a person is born with a mutated, or abnormal, TAZ1 (or G4.5) gene. This abnormal gene is located on the X chromosome, which is a sex-determining chromosome. Males have one X and one Y chromosome, while females have two X chromosomes.

Inheritance: The mutated TAZ1 gene is passed down as an X-linked recessive trait. Since males have only one X chromosome, they will develop the disorder if they inherit just one copy of the mutated gene.

Females, on the other hand, would need to inherit two copies of the mutated gene (one in each of their two X chromosomes) in order to develop Barth syndrome. Although this could theoretically happen, there have been no reports of females who have Barth syndrome. Instead, females are typically carriers of Barth syndrome. This means that a female can have one copy of the mutated gene without experiencing symptoms of Barth syndrome.

Even though a mother who carries the mutated gene does not have the disorder, she can pass her mutated gene to each of her children. There is a 50% chance that a female carrier will pass her X chromosome to a son, and her son will develop the disorder. If the woman has a daughter, there is a 50% chance that the girl will be a carrier.

If a father has Barth syndrome, there is a 100% chance that each of his daughters will carry the mutated gene. Carriers can then pass their mutated genes to their children.

General: If Barth syndrome is suspected, medical tests, such as a urine analysis and complete blood count, may be performed. If these tests indicate Barth syndrome, a diagnosis can be confirmed with DNA testing. Other tests, such as an echocardiogram, may be performed to determine the severity of the condition.

Urine analysis: Most patients with Barth syndrome will have elevated levels of an organic acid, called 3-methylglutaconic acid, in their urine.

Complete blood count: A doctor may take a sample of the patient's blood to determine if he/she has low levels of neutrophils in his/her blood.

DNA test: A DNA test may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the presence of a mutated TAZ1 gene. If a mutation is present, a positive diagnosis is made.

If a female has a family history of Barth syndrome, a DNA test may be performed to determine if she carries a copy of the mutated TAZ1 gene. Although a carrier does not have Barth syndrome, she may pass a copy to her children.

Prenatal DNA testing: If a parent is a carrier of the mutated TAZ1 gene, prenatal testing may be performed at a hospital to determine if the fetus has the disorder. These types of tests are considered outpatient procedures. However, there are serious risks associated with prenatal tests, including miscarriage. Patients should discuss the potential health benefits and risks associated with these procedures before making any medical decisions.

During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus. A small amount of amniotic fluid is removed from the sac surrounding the fetus. The fluid is then analyzed for a mutated TAZ1 gene. This test is performed after 15 weeks of gestation. The risk of miscarriage ranges from one out of 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.

During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta during early pregnancy. Depending on where the placenta is located, CVS can be performed through the cervix or through the abdomen. The tissue sample is then analyzed for a mutated TAZ1 gene. This procedure may be performed between the ninth and 14th week of gestation. The risks of infection or fetal damage are slightly higher than the risks of amniocentesis. Miscarriage occurs in about two percent of women who undergo this procedure.

Genetic counseling: Before and after genetic testing, it is recommended that people meet with genetic counselors. These professionals can help patients understand the risks of having a child with Barth syndrome. A genetic counselor can also explain the different types of genetic tests, including their potential risks and benefits. These counselors can also help patients understand the results and limitations of these tests.

Echocardiogram: An echocardiogram may also be performed to detect possible abnormalities in the heart muscle. This test is similar to an ultrasound that is used in pregnant women. A wand-like device (called a transducer) is rubbed on the patient's chest and sound waves produce images of the heart.

General: Most people with Barth syndrome experience all of the symptoms listed below. However, some people may have only a few of these abnormalities and, as a result, they are often misdiagnosed.

Cardiomyopathy: As infants, patients typically have cardiomyopathy, a condition that occurs when the heart is enlarged and unable to pump efficiently. Common symptoms of cardiomyopathy include difficulty breathing, poor appetite, irregular heartbeat, and slow weight gain.

Metabolism: The mitochondria, cellular structures which produce energy for cells, do not function properly in people with Barth syndrome. This is because a genetic mutation prevents the mitochondria from making enough of a lipid called tetralinoleoyl-cardiolipin. This is the main phospholipid of the mitochondrial inner membrane. Thus, patients with Barth syndrome typically have high levels of an organic acid, called 3-methylglutaconic acid, in their bodies.

Musculoskeletal: People born with Barth syndrome typically have delayed motor skills, reduced muscle tone (called hypotonia), and delayed growth, all of which may lead to varying degrees of physical disabilities.

Weakened immune system: People with Barth syndrome have weakened immune systems because they are born with abnormally low levels of white blood cells, called neutrophils. When there are not enough of these cells in the body, the condition is called neutropenia. Neutrophils make up 70% of all white blood cells in the body and are especially important in fighting off infections and diseases. Therefore, people with neutropenia have an increased risk of becoming sick.

Other: People with Barth syndrome typically experience chronic fatigue, low blood sugar levels (called hypoglycemia), diarrhea, and varying degrees of learning disabilities.

Blood clots: Cardiomyopathy makes patients more likely to develop blood clots. These blood clots may block blood vessels and block blood flow to important organs, including the brain, heart, and lungs. If blood flow to the heart is blocked, it may lead to a heart attack, and if blood flow to the brain is blocked, it may cause a stroke.

Cardiac arrest: Cardiomyopathy may cause irregular heartbeats. Sometimes the heart may beat too slowly to properly circulate blood throughout the body. Sometimes the heart beats too quickly to allow the heart to beat efficiently. Abnormal heartbeats may result in fainting. In serious cases, irregular heartbeats may cause the heart to suddenly stop beating (called cardiac arrest), and the patient is at risk of dying.

Heart failure: People with Barth syndrome typically have cardiomyopathy. Their hearts are enlarged and unable to pump as efficiently as healthy people. This increases the risk of experiencing heart failure, a degenerative condition that occurs when the heart is unable to beat efficiently and pump enough blood to meet the body's needs. Unlike cardiac arrest, which occurs when the heart suddenly stops working, heart failure is a long-term condition that generally worsens over time.

Severe infections: People with Barth syndrome have weakened immune systems because they have low levels of neutrophils in their blood. As a result, they have an increased risk of developing infections, which may be severe. If an infection enters the bloodstream, it may spread to vital organs and become a life-threatening condition.