Barth Syndrome Trust logo

Saving lives through education, advances in treatment and finding a cure for Barth syndrome

Barth Syndrome Trust image

Barth Syndrome Trust image



Barth syndrome (BTHS) is an inborn error of phospholipid metabolism affecting males. ICD Code for Barth Syndrome ICD-10 E7871/E78.71 



  • Dilated cardiomyopathy (DCM) (and sometimes hypertrophic cardiomyopathy [HOCM]), congestive cardiac failure, left ventricular noncompaction (LVNC), endocardial fibroelastosis (EFE), ventricular arrhythmias (ventricular tachycardia or ventricular fibrillation), fetal cardiomyopathy causing miscarriage and stillbirth, neonatal cardiomyopathy
  • Skeletal myopathy, delayed motor milestones, waddling gait, exercise intolerance
  • Feeding problems and Growth Delay: often requiring nasogastric tube feeding or gastrostomy feeding; savoury food fads, vomiting, episodic diarrhoea, rapid growth in late adolescence
  • Neutropenia: low numbers of the white cells which fight bacterial and fungal infections). Neutropenia may be chronic, cyclical or intermittent, mild to severe, and may not be present at all in some cases. Symptoms associated with neutropenia include mouth ulcers, malaise and infections
  • Hypoglycaemia (low blood sugar) and /or lactic acidosis: particularly in babies and infants
  • Cardiolipin abnormalities and Organic aciduria


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).


Clinical presentation

Clinical presentation is highly variable. Most children will develop DCM during the first decade, generally during the first year of life, which may be accompanied by endocardial fibroelastosis (EFE) and/or left ventricular noncompaction (LVNC). It may start in utero, causing cardiac failure, fetal hydrops and miscarriage or stillbirth during the 2nd/3rd trimester of pregnancy. Ventricular arrhythmia, especially during adolescence, can lead to sudden cardiac death. There is a significant risk of stroke. Skeletal (mostly proximal) myopathy causes delayed motor milestones, hypotonia, severe lethargy or exercise intolerance. There is a tendency to hypoglycemia during the neonatal period. Ninety percent of patients show mild to severe intermittent or persistent neutropenia with a risk of septicaemia, severe bacterial sepsis, mouth ulcers and painful gums. Lactic acidosis and mild anaemia may occur. Affected children usually show delayed puberty and growth delay that is observed until the late teens or early 20s, when a substantial growth spurt often occurs. Patients may also present severe difficulties with adequate food intake. Episodic diarrhoea is common. Many patients have a similar facial appearance with chubby cheeks, deep-set eyes and prominent ears.


Genetic and Biochemical Background

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. Defective Taz1p function results in abnormal remodelling of cardiolipin which ultimately compromises mitochondrial structure or respiratory chain function.


Testing for Barth syndrome

Diagnosis was historically based on metabolic screening of urine showing elevated excretion of organic acids (typically 3-methylglutaconic acid (3-MGCA)), followed by TAZ gene sequencing. However, 3-MGC excretion may be normal even in severe cases.


Analysis of the ratio of monolysocardiolipin (MLCL) / cardiolipin (CL) on blood, tissue, fibroblasts or stored neonatal bloodspots is therefore the diagnostic test of choice. Testing is free – click here for details.


Differential diagnosis includes hereditary, dilated and nutritional cardiomyopathy and idiopathic/cyclic neutropenia.


Prenatal diagnosis (chorionic villus biopsy and/or amniocentesis) is possible in families in which the mutation is known.


Transmission is X-linked recessive. A son born to a female carrier has a 50% risk of inheriting the mutation and developing the disease, while a daughter has a 50% risk of being a carrier. All daughters of an affected male will be carriers but none of his sons will be affected.



Treatment is essentially supportive and multidisciplinary. Cardiac failure is treated with conventional drugs or by cardiac transplantation if refractory. The risk of bacterial sepsis in cases of intermittent neutropenia can be reduced by the use of prophylactic antibiotics and/or intermittent use of granulocyte-colony stimulating factor (G-CSF). Difficulties in feeding may necessitate nasogastric or gastrostomy tube feeding. Prognosis has greatly improved with early detection and improvements in treatment and management. Patients are already surviving into their 50s and are expected to live beyond this age.


Written by

Dr Colin Steward, PhD, FRCP, FRCPCH, Royal Hospital for Children, Bristol, England.

Barth Syndrome Trust graphic


Patient in crisis?

Need information about treating a patient?


Let us put you in touch with a clinician who has treated multiple patients with BTHS.

Barth Syndrome Trust graphic
Barth Syndrome Trust graphic
Barth Syndrome Trust graphic