Barth syndrome

Barth syndrome is caused by changes in the tafazzin (TAZ) gene, which is also associated with a heart condition called isolated left ventricular noncompaction (LVNC). The tafazzin gene contains instructions for the tafazzin protein, which is located in mitochondria, the energy-producing cells in the body. Many of these cells are found in the heart. Tafazzin protein is involved in altering cardiolipin, which plays a critical role in the mitochondrial inner membrane. Cardiolipin is a lipid (a type of fat) that can only be found in the mitochondria.

Once a boy or man is found to have Barth syndrome, others in his family could also have the condition or be carriers. If a boy or man is diagnosed with Barth syndrome, his mother may be a carrier. She should be offered genetic testing to see if she is a carrier. If she is a carrier, others in the family (such as her other children (if she has them), her sisters, her brothers, her parents) should be offered the option of genetic testing. To discuss arranging genetic testing for Barth syndrome, speak to your doctor of contact a local genetic counselor. In the U.S., you can find a genetic counselor through the "Find a Genetic Counselor" website at http://www.nsgc.org/page/find-a-genetic-counselor (available through the National Society of Genetic Counselors).

Speak to your doctor about getting a referral to specialists that care for people with Barth syndrome. These include:

Specific strategies for navigating life with a boy who has Barth syndrome can be very helpful. These include things like coping with pain, empowering siblings, and instilling hope. The Barth Syndrome Foundation has plenty of details in a fact sheet.

Boys with Barth syndrome may have very low blood sugar (hypoglycemia), so may need to eat meals more often. Infants and young boys may also benefit from eating raw (uncooked) cornstarch before long periods of fasting (such as overnight). More details are available from the Barth Syndrome Foundation in a document called "Cornstarch" available at https://www.barthsyndrome.org/barthsyndrome/familyresources/factsheets.html. Discuss all of this with your doctor before making any diet changes for your child or yourself.

Heart disease and the risk for infection bring the greatest risk for mortality and morbidity in people with Barth syndrome. If either of these are severe enough, life expectancy can be limited to the first few years of life. Improvements in medical care have increased this, and one 2013 study showed that a risk for early mortality seemed to peak in the first few years of life. New treatments and increased awareness continue to keep people with Barth syndrome healthy.

Barth syndrome is a relatively rare but serious genetic condition that usually affects boys and men. As of 2017, the best estimate is that it occurs in 1 in 300,000 U.S. births. Barth syndrome usually causes abnormalities with the heart, immune system, muscles, and growth. The condition is known to affect the mitochondria, so it is considered a mitochondrial disease. Mitochondria are important parts within a cell and are responsible for producing energy and other functions.

Barth syndrome is caused by changes in the tafazzin (TAZ) gene. More people are using the full name tafazzin when referring to this gene, due to another gene with the same abbreviation (not related to Barth syndrome). Tafazzin gene changes are also associated with a heart condition called isolated left ventricular noncompaction (LVNC), but this occurs rarely. The tafazzin gene contains instructions for the tafazzin protein, which is located in mitochondria, the energy-producing parts of cells in the body. Tafazzin protein is involved in altering cardiolipin, which plays a critical role in the mitochondrial inner membrane. This problem also causes certain compounds to build up in the body, such as 3-methylglutaconic acid (3-MGC) and monolysocardiolipins (MLCL).

Due to issues related to heart failure, fatigue, complications related to neutropenia (and other issues), boys with Barth syndrome can have complex nutrition issues. Specific tips for infants/children/young adults can be very helpful. The Barth Syndrome Foundation has details in a document called "Nutrition Facts in Barth Syndrome" available at https://www.barthsyndrome.org/barthsyndrome/familyresources/factsheets.html.

Boys and men with Barth syndrome may experience the condition differently, but the common symptoms are:

Young boys and all males with Barth syndrome are unique in their symptoms, but most commonly they have:

Teenage boys with Barth syndrome can be unique in their symptoms, but most commonly they have:

An increased risk for infections is common in people with Barth syndrome and can be serious. Boys with Barth syndrome may have frequent mouth infections, mouth ulcers, lung infections (pneumonia), or blood infections. Not everyone has all of these symptoms, or has them to the same extent. Being extra careful about germs and maintaining daily hygiene is very important for people with Barth syndrome.

Most commonly, the heart problems found in people with Barth syndrome are dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), or left ventricular noncompaction (LVNC). This can cause the heart muscle to become weak and not work properly. These can progress or even change over time, and may cause trouble with heart function or rhythm, causing congestive heart failure or even sudden death. Not everyone has all of these heart problems, or has them to the same extent.

A specific medical care plan is essential to keeping people with Barth syndrome healthy. Referrals to medical specialists are needed to help with this. The following are recommended after a diagnosis is first made, which you should discuss with your doctor:

Certain medicine should be avoided if you have Barth syndrome. A MedicAlert bracelet can be very helpful to let others know about this. These include:

As of 2019, Barth syndrome is not on the core condition Recommended Uniform Screen Panel (RUSP) list in the U.S. However, it is on the secondary conditions list. The RUSP is created by the U.S. Health Resources and Services Administration, and states use this list to guide what conditions they screen for on newborn screening. Being a secondary condition means that Barth syndrome can be picked up by the newborn screening test because it is in the differential diagnosis of a core condition. For instance, the newborn screening test may screen positive for a core condition. However, when further testing is done for the core condition, the baby would test negative. The abnormal original screen may alert physicians to order further testing that includes testing for Barth syndrome.

Getting tested for Barth syndrome can happen in different ways. It may include laboratory testing in combination with a physical exam with a doctor looking for signs/symptoms of the condition. Laboratory tests can show high levels of 3-methylglutaconic acid (3-MGA) in urine or blood, as well as increased monolysocardiolipins (MLCL) and decreased cardiolipins (L4-CL). Genetic testing (usually from a blood sample) for the gene that causes Barth syndrome, known as tafazzin (TAZ), is also possible. Genetic laboratories can study the entire tafazzin gene DNA sequence to look for mutations that may cause Barth syndrome. To discuss arranging genetic testing for Barth syndrome, speak to your doctor of contact a local genetic counselor. In the U.S., you can find a genetic counselor through the "Find a Genetic Counselor" website at http://www.nsgc.org/page/find-a-genetic-counselor (available through the National Society of Genetic Counselors).

As of September 2017, the Barth Syndrome Foundation lists several opportunities to enroll in research about Barth syndrome. Visit the Barth Syndrome Foundation website for more details at https://www.barthsyndrome.org/research. Other agencies, such as the National Institutes of Health in the U.S. also have relevant research to those with Barth syndrome. Details can be found at https://www.ninds.nih.gov/Disorders/All-Disorders/Barth-Syndrome-Information-Page. As of June 2019, clinical trials were available and information can be found at the ClinicalTrials.gov website at https://clinicaltrials.gov/.

As of September 2017, there is no FDA-approved treatment for Barth syndrome. Treatments to manage certain symptoms of Barth syndrome are available, and each person needs them differently. The Barth Syndrome Foundation lists several opportunities to enroll in research about Barth syndrome. Visit the Barth Syndrome Foundation website for more details at https://www.barthsyndrome.org/living-with-barth-syndrome/-opportunities-to-participate-in-barth-syndrome-research. Other agencies, such as the National Institutes of Health in the U.S. also have relevant research to those with Barth syndrome. Details can be found at https://www.barthsyndrome.org/science–medicine/nih-and-other-agencies-research-initiatives-relevant-to-barth-syndrome. Clinical trials are currently available and information can be found at the ClinicalTrials.gov website at https://clinicaltrials.gov/.

Barth syndrome is considered a mitochondrial disease, specifically a mitochondrial myopathy (a disease that particularly affects the muscles). This is because Barth syndrome is caused by changes in the tafazzin TAZ gene. More people are using the full name (tafazzin) when referring to this gene, due to another gene with the same abbreviation (not associated with Barth syndrome). The tafazzin gene contains instructions for the tafazzin protein, which is located in mitochondria, the energy-producing cells in the body. Tafazzin protein is involved in altering cardiolipin, which plays a critical role in the mitochondrial inner membrane. Cardiolipin is a lipid (a type of fat) that can only be found in the mitochondria. This problem also causes certain compounds to build up in the body, such as 3-methylglutaconic acid (3-MGC) and monolysocardiolipins (MLCL).

Barth syndrome is inherited in an X-linked recessive manner. This means the gene associated with it, called tafazzin (TAZ), is on the X-chromosome. Females usually have two X-chromosomes and males have one. People with Barth syndrome have a change, or mutation, in the tafazzin gene on one of their X-chromosomes. Since males only have one X-chromosome to begin with, they are more likely to have symptoms of Barth syndrome if they have a tafazzin gene mutation — they have no "back-up" gene on a second X-chromosome. Females have that "back-up" second X-chromosome and are often protected from symptoms of Barth syndrome for this reason. Females who have a tafazzin gene mutation on one of their X-chromosomes are known as Barth syndrome "carriers" and can have sons with Barth syndrome and daughters that are Barth syndrome carriers in the future.

There are some strategies to consider when working with multiple medical specialists for different medical appointments. This includes ideas like keeping copies of all your child’s records, sharing information, and asking lots of questions. More information is available from the Barth Syndrome Foundation in a document called "Practical Tips for Individuals with Barth Syndrome" that is available at https://www.barthsyndrome.org/barthsyndrome/familyresources/factsheets.html.

Specific strategies may be helpful when speaking to your child’s school about your son having Barth syndrome. You can discuss academic issues, social issues, practical issues, in-school health issues and make a request for regular team meetings. For boys with Barth syndrome in kindergarten and higher grades, there can be challenges with mathematics and some visual-spatial skills. There may also be some speech delay/concerns. Additionally, fatigue is often an issue preventing individuals with Barth syndrome from completing a school day like their peers.

More information is available from the Barth Syndrome Foundation.

Young adults with Barth syndrome may need help and support when it comes to transitions in their health care, schooling, employment, and beyond. Teaching them about these issues can foster independence in all of these areas. Global Genes Toolkit has information about transitioning to adult care. The Barth Syndrome Foundation also has a fact sheet.

Speak to your doctor about getting a referral to specialists that care for people with Barth syndrome. These include:

Getting tested for Barth syndrome can happen in different ways. It may include laboratory testing in combination with a physical exam with a doctor looking for signs/symptoms of the condition. Laboratory tests can show high levels of 3-methylglutaconic acid (3-MGA) in urine or blood, as well as increased monolysocardiolipins (MLCL) and decreased cardiolipins (L4-CL). Genetic testing (usually from a blood sample) for the gene that causes Barth syndrome, known as tafazzin (TAZ), is also possible and recommended. Genetic laboratories can study the entire tafazzin gene DNA sequence to look for mutations that may cause Barth syndrome. To discuss arranging genetic testing for Barth syndrome, speak to your doctor of contact a local genetic counselor. In the U.S., you can find a genetic counselor through the "Find a Genetic Counselor" website at http://www.nsgc.org/page/find-a-genetic-counselor (available through the National Society of Genetic Counselors).

As of September 2017, the Barth Syndrome Foundation lists several opportunities to enroll in research about Barth syndrome. Visit the Barth Syndrome Foundation website for more details at https://www.barthsyndrome.org/research. Other agencies, such as the National Institutes of Health in the U.S. also have relevant research to those with Barth syndrome. Details can be found at https://www.ninds.nih.gov/Disorders/All-Disorders/Barth-Syndrome-Information-Page. As of June 2019 clinical trials were available and information can be found at the ClinicalTrials.gov website at https://clinicaltrials.gov/.

Barth syndrome is estimated to occur in 1 in 300,000 U.S. births. Fewer than 10 new patients may be diagnosed with Barth syndrome in the U.S. each year. Studies in England and South Wales suggest the incidence may be as high as 1 in 130,000 births. More than 150 cases has been reported in the scientific literature.

Partnering with your child’s school to discuss Barth syndrome can be very helpful, as issues can come up in terms of health and academic concerns. Regular team meetings can also be effective. The Barth Syndrome Foundation has information and resources to help you with this.

Rectal thermometers in those with a weakened immune system (neutropenia)
Medicines with succinylcholine (certain non-depolarizing neuromuscular blockers could have a prolonged effect) — a MedicAlert bracelet is needed
Human growth hormone is discouraged, as most boys with Barth syndrome reach normal stature by adulthood
Medicines with sevoflurane use can cause an increased risk for malignant hyperthermia — a MedicAlert bracelet is needed

You can learn more about getting a MedicAlert bracelet by visiting their website at https://www.medicalert.org/.

Other names for Barth syndrome include:

In the U.S., the Barth Syndrome Foundation advocates for people with the condition, and their website is https://www.barthsyndrome.org/home. In Canada, the Barth Syndrome Foundation of Canada leads this work and is available at http://www.barthsyndrome.ca/home.