What is Barth syndrome? #MentalHealthAwareness

Posted by Sukant Khurana
February 8, 2018

NOTE: This post has been self-published by the author. Anyone can write on Youth Ki Awaaz.


By Rashi Jain, Farooq Ali Khan, Abhishek Kumar, Raamesh Gowri Raghavan, and Sukant Khurana

Photo by Kelly Sikkema on Unsplash

What is Barth syndrome?

Barth syndrome is a rare, metabolic, and neuromuscular, genetic disorder that occurs exclusively in males, since it is passed from mother to son through the X chromosome. Although Barth syndrome typically becomes apparent during infancy or early childhood, the age of onset, associated symptoms and findings, and disease course varies considerably, even among affected members of the same family (kindred). Primary characteristics of the disorder include an enlarged and weakened heart (dilatedcardiomyopathy and skeletal muscle (cardioskeletal myopathy), low levels of certain white blood cells (neutrophils, neutropenia) that help to fight bacterial infections, and growth retardation, potentially leading to short stature. The disorder is also associated with increased levels of certain organic acids in the urine and blood, such as 3-methylglutaconic aciduria/acidemia.

The left ventricle of the heart may show increased thickness as a result of unusually high concentrations of elastic, collagenous fibers (endocardial fibroelastosis). The thickening reduces the ability of the left ventricle to push blood though to the lungs and thus is the prime source of potential heart failure.


Symptoms associated with Barth syndrome may be evident at birth (congenital), or infancy, or early childhood. Yet, on rare occasions the disorder may not be diagnosed until adulthood.

Most individuals with Barth syndrome present with weakened heart muscle (cardiomyopathy) that leads to the enlargement (dilation) of the heart’s lower chambers (ventricles). Known as dilated cardiomyopathy, signs of this condition are often present at birth (congenital), or may appear during the first months of life. Dilated endocardial myopathy, typically weakens the heart’s pumping action, reducing the volume of blood circulating to the lungs and the rest of the body (heart failure). Symptoms of heart failure may depend on the child’s age and other factors. In young children, for example, heart failure may be manifest as fatigue and shortness of breath (dyspnea)with exertion.

Barth syndrome is also associated with abnormally diminished muscle tone (hypotonia), and muscle weakness (skeletal myopathy), that often leads to delays in the acquisition of gross motor skills. Gross motor skills include such activities as crawling, walking, running, jumping, and maintaining balance. These are the skills that require the use and coordination of large muscle groups. Weakness of the facial muscles may lead to unusual facial expressions.

In addition, affected infants and children may fail to thrive, and fail to gain weight at the expected rate. They may have mild learning disabilities, (although they are usually of normal intelligence), and, in many cases, may be prone to recurrent bacterial infections due to low levels of circulating neutrophils in the blood. Without prompt detection and appropriate treatment, heart failure and bacterial infections can be life-threatening complications.

In addition to abnormalities of heart and skeletal muscle, neutropenia, and growth retardation, patients with Barth syndrome have a specific biochemical marker that has been recognized for many years as a primary indicator of Barth syndrome. A biochemical marker is any substance, such as an enzyme or small molecule, that is detected in urine or other body fluids and serves as a diagnostic sign of a particular disorder. Researchers have shown that individuals with Barth syndrome have abnormally increased levels of 3-methylglutaconic acid in the urine and in the liquid portion of the blood. According to clinicians, children with Barth syndrome may have elevated blood levels of 3-methylglutaconic acid from mid-infancy up to about age three. There does not appear to be an association, however, between the increased acid levels and the severity of other symptoms and signs associated with Barth syndrome.

Viewed by the microscope, the heart muscle cells of patients with Barth syndrome have abnormally shaped mitochondria. Other metabolic signs that are not diagnostic themselves but serve to support a diagnosis based on other criteria are, high blood and urine levels of lactic acid (a by-product of intense muscular activity) and low carnitine levels. Carnitine plays a role in the movement of chemicals, especially fatty acids, across the cell membrane.


Barth syndrome is transmitted as an X-linked recessive trait. A gene responsible for the disorder has been located on the long arm (q) of chromosome X at Xq28.

The gene located at chromosome X28 is known as the TAZ gene. The TAZ gene codes for a group of proteins called taffazins, that serve at least two functions. First, these proteins play a role in the maintenance of the inner, much-folded, membranes of the mitochondria in cells. The mitochondria are the energy-producing factories upon which the cell depends. The taffazins serve to assure that the concentration of a specific fat (cardio-lipin) is sufficient to maintain energy production in the mitochondria. Taffazins also promotes the development of bone cells from the precursor cells of bone (osteoblasts).

TAZ gene mutations result in the production of tafazzin proteins with little or no function. As a result, tafazzin cannot alter cardiolipin. It is also responsible for the appearance of 3-methylglutaconic acid in the Barth patient’s blood and urine. A lack of functional cardiolipin impairs normal mitochondrial shape and functions. Tissues with high energy demands, such as the heart and skeletal muscles, are most susceptible to cell death due to reduced energy production in mitochondria. Additionally, abnormally shaped mitochondria are found in affected white blood cells, which could affect their ability to grow (proliferate) and mature (differentiate), leading to neutropenia. Dysfunctional mitochondria likely lead to other signs and symptoms of Barth syndrome.


Barth syndrome may be diagnosed during infancy or early childhood (or, in some cases, at a later age), based upon :

· a thorough clinical evaluation,y

· identification of characteristic physical findings,

· a complete patient and family history,

· and a variety of specialized tests.

Experts indicate that a diagnosis of Barth syndrome should be considered for any male infant or child with dilated cardiomyopathy of unknown cause (idiopathic); low levels of circulating neutrophils (neutropenia); elevated urinary levels of 3-methylglutaconic acid (aciduria); abnormal mitochondria within heart muscle; and/or muscle abnormalities (myopathy) of unknown cause that occur in association with growth retardation.

For infants and children with signs of cardiomyopathy, metabolic screening tests should be conducted, including studies to measure levels of 3-methylglutaconic acid and other organic acids in the urine and blood. Anelevated urinary level of 3-methylglutaconic acid (3-methylglutaconic aciduria) has been recognized as a biochemical marker that may function as a diagnostic sign of Barth syndrome. It is important to measure the concentration of neutrophils in the blood. Persistent low levels of neutrophils help confirm the diagnosis in combination with these other signs. Prenatal and postnatal testing for the presence of the TAZ gene is available at a few genetic laboratories.


The treatment of Barth syndrome is directed toward the specific symptoms that are apparent in each individual. Such supportive treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; physicians who specialize in childhood heart disease (pediatric cardiologists); specialists in the study of the blood and blood-forming tissues (hematologists); specialists in the treatment of bacterial infections, physical therapists; occupational therapists; and/or other health care professionals.

Heart failure and/or bacterial infections are the more grave threats to a patient. Many infants and children with Barth syndrome require therapy with diuretic and digitalis medications to treat heart failure. Evidence suggests that many affected children may be gradually removed from such cardiac therapy during later childhood due to improvement of heart functioning.

For affected individuals with confirmed neutropenia, complications due to bacterial infection are often preventable by ongoing monitoring and early therapy of suspected infections with antibiotics. For example, antibiotics may be provided as a preventive (prophylactic) therapy during neutropenia to prevent the onset of infection. For some individuals with neutropenia, such as those with repeated bacterial infections and neutrophil levels that are persistently below 500, physicians may recommend the use of agents that stimulate the bone marrow’s production of white blood cells.

Genetic counseling will also benefit affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.


Barth syndrome is not curable and there is no specific model of treatment for the condition. The main problem with Barth syndrome is that involves or causes a number of conditions, many of which can cause complications that are life threatening. Treatment is aimed at managing each of these conditions to improve quality of life and lower the risk of fatality.

· Antibiotics are used in the treatment of infections that result because of neutropenia. Drugs are also used to stimulate and encourage the production of white cells to help prevent and fight infections.

· Medications are also prescribed to treat various heart problems as and when they emerge.

· Carnitine, a dietary supplement is occasionally used in treatment as it has helped some children, but there are also cases where it has worsened muscle weakness and even accelerated heart failure.


Barth syndrome appears to affect all ethnic groups. Epidemiologists at Johns Hopkins University Medical Center estimate the incidence of this syndrome to be somewhere between 1 in 200,000 to 400,000 births. More than 150 cases have been described in the scientific literature.

Availability of medicines

There is no cure or specific treatment for Barth syndrome. Treatment focuses on reducing symptoms and preventing complications, such as infections.

· Physical therapy to help babies who have reduced muscle tone as a result of Barth syndrome

· Antibiotics to treat bacterial infections

· Lifestyle changes Your doctor may advise a low-salt diet, and that your child maintains a healthy weight.

· Heart medications

· Artificial pacemaker

· Heart transplant

There are no sureshot drugs prescribed for barth syndrome, some integrative therapies have been studied as possible treatments for symptoms commonly associated with the disorder.

· Coleus: The root extract of coleus is known as forskolin. Forskolin may improve cardiovascular function in patients with cardiomyopathy. However, additional study is needed to confirm these findings.

· Ginseng: A small number of studies report that ginseng may stimulate the immune cells in the body, improve the effectiveness of antibiotics in people with acute bronchitis, and enhance the body’s response to flu vaccines. It is promising but again as with extracts, quality of regulation needs improvement.

· Zinc: Zinc appears to be an essential element that the immune system needs to function properly. Zinc gluconate appears to have beneficial effects on immune cells, improving CD3 and CD4 counts and increasing CD4/CD8 ratios in children. .

· Astragalus: In traditional Chinese medicine (TCM), astragalus is commonly found in mixtures with other herbs. Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research and in traditional accounts. Reliable human studies are lacking. High-quality human research is necessary before a firm conclusion can be drawn.

· Beta-carotene: Beta-carotene is a member of the carotenoids, which are very colorful (red, orange, yellow), fat-soluble compounds. They are naturally found in many fruits, grains, oils, and vegetables (e.g. green plants, carrots, sweet potatoes, squash, spinach, apricots, and green peppers). Preliminary research of beta-carotene for immune system maintenance or stimulation shows mixed results. Further research is needed before a conclusion can be drawn.

· Avoid if sensitive to beta-carotene, vitamin A, or any other ingredient in beta-carotene products (e.g. gelatin).

· Bovine colostrum: Bovine colostrum is the pre-milk fluid produced from cow breast glands during the first two to four days after birth. Bovine colostrum contains proteins called immunoglobulin antibodies that are involved in the immune response. It has been suggested that bovine colostrum may improve immune function. However, further research is needed before a firm conclusion can be made.

· Coenzyme Q10: Coenzyme Q10 (CoQ10) is produced by the human body and is necessary for basic functioning of cells. There is conflicting evidence from research on the use of CoQ10 in patients with dilated or hypertrophic cardiomyopathy. Better research is needed in this area before a recommendation can be made.

· Echinacea: Extracts of Echinacea species have attracted recent scientific interest because they may have immune stimulant properties. Echinacea has been studied alone and in combination with other herbs and supplements for immune system stimulation (including in patients receiving cancer chemotherapy). It remains unclear if this is an effective treatment. Additional studies are needed in this area before conclusions can be drawn regarding safety or effectiveness..

· Gamma linolenic acid (GLA): Gamma linolenic acid (GLA) is a dietary fatty acid that is found in many plant oil extracts. Commercial products are typically made from seed extracts from evening primrose (average oil content 7–14%), blackcurrant (15–20%), borage oil (20–27%), and fungal oil (25%). Few clinical trials have investigated the effect of GLA on immune responses in healthy human subjects. GLA, as blackcurrant seed oil, may offer some benefits. Further study is required before a definite conclusion can be made.

· Goldenseal: Goldenseal is one of the five top-selling herbal products in the United States. However, there is little scientific evidence about its safety or effectiveness. Goldenseal has sometimes been suggested as an immune system stimulant. However, there is little human or laboratory evidence available in this area. More research is needed before a firm conclusion can be drawn..

· Maitake: Maitake mushrooms (Grifola frondosa) are fungi that can be eaten. Animal and laboratory studies suggest that beta-glucan extracts from maitake may alter the immune system. However, reliable studies in humans are currently not available.

· Massage: Preliminary evidence suggests that massage therapy may preserve immune function. Further research is needed before a firm conclusion can be made.

· Meditation: Various forms of meditation have been practiced for thousands of years throughout the world, with many techniques originating in Eastern religious practices. Preliminary research reports increased antibody response after meditation. Further study is needed to confirm these findings.

· Probiotics: Probiotics are beneficial bacteria and are sometimes called friendly germs. They help maintain a healthy intestine and aid in digestion. Most probiotics come from food sources, especially cultured milk products. Probiotics can be taken as capsules, tablets, beverages, powders, yogurts, and other foods. A type of probiotic, called Lactobacillus, which is found in fermented milk, low-fat milk, and lactose-hydrolyzed low-fat milk, may enhance immune function. Another probiotic, called Bifidobacterium, has been studied in the elderly and it may have similar effects. However, commercially produced yogurt may not yield similar benefits. There is some evidence that probiotics added during food preparation (e.g., waffles with Enterococcus faecium M-74 added) can enhance immune functioning. More studies are needed, particularly with yogurt, before a firm conclusion can be made..

· Thymus extract: Thymus extracts for nutritional supplements are usually derived from young calves (bovine source). Preliminary evidence suggests that thymus extract may increase left ventricular function, exercise tolerance, and survival. Additional study is needed to determine if thymus extract is an effective treatment for cardiomyopathy.

· Vitamin A: Vitamin A is a fat-soluble vitamin, which is derived from two sources: retinoids and carotenoids. Retinoids (e.g. retinal and retinoic acid) are found in animal sources, including the liver, kidney, eggs, and dairy products. Carotenoids (e.g. beta-carotene) are found in plants, including dark or yellow vegetables and carrots. Vitamin A deficiency may weaken the immune system, but there is no clear evidence that additional vitamin A supplementation is beneficial for immune function in patients who are not vitamin A deficient.

· Vitamin B6: Major sources of vitamin B6 include cereal grains, legumes (beans), vegetables (e.g. carrots, spinach, peas), potatoes, milk, cheese, eggs, fish, liver, meat, and flour. Vitamin B6 is important for immune system function in older individuals. One study found that the amount of vitamin B6 required to reverse weakened immune systems in elderly people was more than the current recommended dietary allowance (RDA). Well-designed clinical trials on vitamin B6 supplementation for this indication are needed before a recommendation can be made.

· Vitamin E: Studies of the effects of vitamin E supplementation on immune system function have yielded mixed results. Further research is needed before a clear conclusion can be drawn.

Case study

Jacob Anthony Wilson was born August 22, 2000 after a normal pregnancy. According to his mother, Amy Wilson, as an infant he had a normal appetite. He was behind on some things but nothing that would indicate that she or his physicians should be alarmed of. Jacob sat up later than other children his age and suffered from recurring ear infections. He had a hard time fighting them off and no one could explain why. Pulling up was more difficult for him due to overall weakness. Jacob started crawling around 8 months of age and began to walk at 14 months. But nothing seemed particularly abnormal until a week after his first birthday.

On August 27, 2001, Jacob suffered his first seizure. This was said to be a febrile seizure caused by virus. Jacob went on to have 5 seizures altogether. On October 29, 2002, at the age of 2, he was hospitalized with an ear infection and low CBC (Complete Blood Count). This started a routine of weekly blood draws at the local children’s cancer clinic located at University of Mississippi Medical Center’s Blair E. Batson Hospital for Children in order to monitor the low CBC’s. His mom, Amy, had lots of fear that something bad was going on that his doctors weren’t finding. After 3 weeks Jacob’s CBC came back up and his mother was just told that Jacob just had more trouble than others fighting off infections. In the meantime, Jacob also had complaints about leg pain. He had an x-ray of his legs done in 2004. He had coxa vara, a deformity of the hip, whereby the angle between the head and the shaft of the femur is reduced to less than 120 degrees. This results in the leg being shortened, and the development of a limp. But the reason for his pain was said to be caused by rheumatoid arthritis. Jacob started treatment and physical therapy. His short stature was addressed in 2007 and endocrinology determined that he should be on growth hormones. Rheumatology also decided to recommend Jacob go to a neurologist because of tight tendons. It was the neurologist who determined Jacob to have a myopathy (muscle weakness). Jacob had a muscle biopsy performed because of myopathy. He now had many different individual diagnoses but no overall explanation. Jacob was brought in to genetics after his first cousin Christopher’s diagnosis of Barth syndrome. Myopathy, unexplained viruses, skeletal problems and questions with his CBCs in the past fit the same diagnosis. Geneticist Omar Abdul- Rahman was now on the case to find the cause of muscle weakness which was apparently affecting boys in the family

Today at the age of 16, Jacob is heart healthy, but in 2010 he had several episodes of arrhythmia. Thankfully he still does not present with cardiomyopathy, one of the common characteristics of Barth syndrome. However, another of Jacob’s struggles are that several bouts of hypoglycemia landed him up in the emergency room. Boys with Barth syndrome are very high risk for hypoglycemia if they haven’t eaten. He has also recently had neutropenia rear its ugly head, causing him to miss a lot of school. Neutropenia is a reduction in neutrophils, a type of white blood cell that is most important for fighting bacterial infections. Neutropenia may predispose an individual to mouth ulcers, fevers and bacterial infections such as bacterial pneumonia and skin abscesses. Jacob doesn’t eat sweets but he craves sour and hot foods. He will eat as much hot sauce as he is allowed. It is much more difficult for him to manage buttons on clothing and keep up with his peers physically. Upon asking Jacob to share some physical and social challenges of having Barth syndrome, his reply was, “I cannot walk that far without my lungs expanding and crushing my ribs and making me tired and drowsy. I cannot hold heavy objects up for very long or carry them very far. Most of my friends don’t get why I’m so small even if I tell them a hundred times, but some of my friends get it, like my friend Michael. He has been there for me for as long as I remember and I appreciate that from him. He believes in me. But because of my size some kids try to take advantage of me and tell me what to do.”

There is no specific treatment for Barth syndrome, but each of the individual problems can be successfully controlled.


Genetic Home Reference- https://ghr.nlm.nih.gov/condition/barth-syndrome#statistics

National Organization for Rare Disorders NORD — https://rarediseases.org/rare-diseases/barth-syndrome/







Dr. Sukant Khurana runs an academic research lab and several tech companies. He is also a known artist, author, and speaker. You can learn more about Sukant at www.brainnart.com or www.dataisnotjustdata.com and if you wish to work on biomedical research, neuroscience, sustainable development, artificial intelligence or data science projects for public good, you can contact him at skgroup.iiserk@gmail.com or by reaching out to him on linkedin https://www.linkedin.com/in/sukant-khurana-755a2343/.

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