The girl presented recurrent episodes of severe acute heart failure, progressive muscle weakness, and had a fatal septic shock at 3years. [zora.uzh.ch]

Growth deficiency was present (mean weight percentile: 15%; mean height percentile: 8%). [ncbi.nlm.nih.gov]

A fever may also be present. Diarrhea and/or constipation. Weak muscle tone may lead to fatigue and difficulty exercising. [news-medical.net]

Clinical description Clinical presentation is highly variable. [orpha.net]

• Mild Clinical Course

  Rigaud et al [2013] estimated an incidence of 1.5 cases per million births (95% CI: 0.2-2.3) based on data from France between 1995 and 2008; they noted, however, that some patients may have been undiagnosed either due to a mild clinical course or sudden [ncbi.nlm.nih.gov]

• Failure to Thrive

  […] to thrive as infants, poor muscle tone, difficulty with fine finger movements and walking, lack of stamina and frequent serious bacterial infections. [nicklauschildrens.org]

  Signs and symptoms of Barth syndrome include: skeletal muscle abnormalities delayed gross motor skill development weak muscle tone frequent infections failure to thrive in infants and other abnormalities in growth exercise intolerance or lack of stamina [childrenshospital.org]

  Such abnormal weight-for-height ratios in Barth syndrome are rarely caused by nutritional failure-to-thrive, but are a "normal" characteristic of Barth syndrome. [web.archive.org]

  These symptoms can include: Heart conditions such as arrhythmias, heart failure, and cardiomyopathy Failure to thrive Delays in meeting developmental milestones Delays in the acquisition of gross motor skills Exercise intolerance Muscle weakness Easily [verywellhealth.com]

  […] to thrive, episodic diarrhea, characteristic facies, and an X-linked family history (Ichida et al., 2001; Steward et al., 2010). [frontiersin.org]

• Palpitations

  Cardiologically, he had never experienced syncope and presented with occasional episodes of chest pain and palpitations. [revespcardiol.org]

  palpitations, syncope), abnormal screening tests, or a family history of sudden death. [ncbi.nlm.nih.gov]

• Chest Pain

  Cardiologically, he had never experienced syncope and presented with occasional episodes of chest pain and palpitations. [revespcardiol.org]

• Proximal Muscle Weakness

  • The clinical manifestations range from prenatal death and stillbirth with hydrops to adult cardiomyopathy and mild proximal muscle weakness with moderate disease impact and neutropenia. • Neutropenia, which is most commonly intermittent and highly [medlink.com]

• Round Face

  Common signs and symptoms include; distinctive facial features with a round face and full cheeks, large ears, deep-set eyes, big chin, heart muscle weakness which presents as heart failure and/or arrhythmias including sudden death, growth delay and failure [nicklauschildrens.org]

  They have a round face with prominent chin and full cheeks. The ears are large, and they have deep set eyes. The facial features become less noticeable with age. [rarediseases.org]

  Younger males with Barth syndrome have a characteristic facial gestalt that is most evident during infancy, characterized by a tall and broad forehead, round face, full cheeks, prominent pointed chin, large ears, and deep-set eyes. [ncbi.nlm.nih.gov]

• Pointed Chin

  Younger males with Barth syndrome have a characteristic facial gestalt that is most evident during infancy, characterized by a tall and broad forehead, round face, full cheeks, prominent pointed chin, large ears, and deep-set eyes. [ncbi.nlm.nih.gov]

Clinical testing and workup As a part of routine follow up, growth and height of the children are monitored regularly. Annual cardiac follow up using ECG, echocardiogram and Holter monitor is considered. [rarediseases.org]

Initial lumbar puncture and sepsis workup were normal. Blood chemistry showed normal values. Pyruvate was initially elevated [2.37 mg/dL (0.36-0-59) ( 262 µmol/L)]. [enlivenarchive.org]

Although diagnostic workup, including bone marrow biopsy, had been negative to date, he began receiving biweekly injections of granulocyte colony stimulating factor with a beneficial effect [8]. [journals.lww.com]

Laboratory workup for neutrophil dysfunctions: numerical and functional defects. J Immunol Methods. 1999 ; 232 : 211 -229. Murdoch C, Finn A. Chemokine receptors and their role in inflammation and infectious diseases. Blood. 2000 ; 95 : 3032 -3043. [dx.doi.org]

The reverse is also true: It may be worth adding cardiac evaluation to the workup of the diagnosis of a chronic neutropenia suspected to be congenital. [ojrd.biomedcentral.com]

• Short PR Interval

  A recent electrocardiogram (ECG) was essentially unremarkable ( Figure 1 ), showing in sinus rhythm a slightly short PR interval (0.12 ms), and mildly high voltage QRS, in particular deep S waves in V1-V2 with ST elevation with an early repolarization [revespcardiol.org]

• ST Elevation

  A recent electrocardiogram (ECG) was essentially unremarkable ( Figure 1 ), showing in sinus rhythm a slightly short PR interval (0.12 ms), and mildly high voltage QRS, in particular deep S waves in V1-V2 with ST elevation with an early repolarization [revespcardiol.org]

Treatment - Barth syndrome Treatment is directed toward the specific symptoms that are apparent in each individual. The treatment of Barth syndrome is generally directed toward the specific symptoms that are apparent in each individual. [checkorphan.org]

Current treatment strategies are merely ameliorative in nature and up to 30% of patients still succumb to the disease early in life. A curative treatment is still an unmet need. [digital.lib.washington.edu]

Management and treatment Treatment is essentially supportive and multidisciplinary. Cardiac failure is treated with conventional drugs or by cardiac transplantation if refractory. [orpha.net]

Secondary endpoints will include other functional assessments (of muscle strength, balance, etc.), patient-reported outcomes, and overall treatment safety. [mitochondrialdiseasenews.com]

Treatment varies depending on symptoms. Research in gene therapy is ongoing with the hope of developing a cure. [diseaseinfosearch.org]

Diagnosis - Barth syndrome Prognosis - Barth syndrome Prognosis has greatly improved with early detection and improvements in treatment and management. Patients are already surviving into their 40s and are expected to live beyond this age. [checkorphan.org]

Prognosis Prognosis has greatly improved with early detection and improvements in treatment and management. Patients are already surviving into their 40s and are expected to live beyond this age. [orpha.net]

Prognosis 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. [brainfacts.org]

Early and accurate diagnosis can help medical treatment and improve prognosis. Despite poor prognosis of Barth syndrome during infancy, patients can survive until adulthood. [revespcardiol.org]

Therefore, early diagnosis and management, with recognition of a wide range of phenotypes, are important for improving the prognosis of Barth syndrome. [ci.nii.ac.jp]

Etiology BTHS is caused by mutations in the TAZ gene (tafazzin; Xq28) which encodes Taz1p acyltransferase involved in the metabolism of cardiolipin, a major phospholipid in inner mitochondrial membranes. [orpha.net]

To evaluate the implication of TAZ gene in the etiology of DCM and left ventricular non-compaction we studied the TAZ gene in 48 DCM and left ventricular non-compaction patients. [revespcardiol.org]

Cardiolipin metabolism and its causal role in the etiology of the inherited cardiomyopathy Barth syndrome. Chem Phys Lipids. 2015;193:1-10. Reynolds S. [rarediseases.org]

Summary Epidemiology Prevalence is estimated at 1/454,000 and incidence at 1/140,000 (South-West England, South Wales) to 1/300,000-1/400,000 live births (USA). BTHS affects male patients. [orpha.net]

Epidemiology 151 living BTHS patients are known to the BSF worldwide in 2012. [ncbi.nlm.nih.gov]

Epidemiology 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. [medium.com]

Phosphokinome Analysis of Barth Syndrome Lymphoblasts Identify Novel Targets in the Pathophysiology of the Disease. Int. J. Mol. Sci. 2018, 19, 2026. [mdpi.com]

Here, we combined patient-derived and genetically engineered induced pluripotent stem cells (iPSCs) with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation [miami.pure.elsevier.com]

This objective fits into our broad goals to understand the function of cardiolipin in mitochondria and to unravel the molecular pathophysiology of BTHS. [grantome.com]

“Because it is a relatively newly diagnosed disease, there is still much to learn regarding its pathophysiology and relation to impaired skeletal muscle and heart function.” [outlook.wustl.edu]

Several model systems for Barth syndrome have been developed to elucidate the disease pathophysiology. Mouse model of Barth syndrome provide new insight into the role of tafazzin. [els.net]

For example, antibiotics may be provided as a preventive (prophylactic) therapy during neutropenia to prevent the onset of infection. Other treatment for this disorder is typically symptomatic and supportive. Resources - Barth syndrome [checkorphan.org]

This phenotype can be genetically suppressed by inactivation of the gene encoding a calcium-independent phospholipase A(2), iPLA2-VIA, which also prevents cardiolipin depletion/monolysocardiolipin accumulation, although in wild-type flies inactivation [ncbi.nlm.nih.gov]

Preventative daily antibiotics will reduce the risk of bacterial infection if boys are severely neutropenic. [contact.org.uk]

For example, antibiotics may be provided as a preventive (prophylactic) therapy during neutropenia to prevent the onset of infection. Giving uncooked cornstarch before bedtime is recommended to prevent muscle loss. [rarediseases.org]

Treatment is focused on reducing symptoms and preventing complications. [nicklauschildrens.org]