Barth syndrome

Background

Barth syndrome is a genetic condition that mostly affects males. The main problems are heart muscle weakness (see entry Cardiomyopathies) and neutropenia (low numbers of white blood cells called neutrophils) leading to bacterial infections. The disease is very variable: many boys will develop heart failure as neonates or infants but this may also develop in the womb (causing recurrent late miscarriage or stillbirth). However, some patients may simply have weak muscles and others are never neutropenic. The disease may be confused as a mitochondrial disease (see entry Mitochondrial diseases) where no mutation of mitochondrial genes can be found.

Other features include growth delay, muscle weakness, lethargy, fatigue, delayed motor milestones, poor feeding, hypoglycaemia (low blood sugar), lactic acidosis (excess lactic acid in the blood), excess of a chemical called 3-methylglutaconic acid in urine and cardiac rhythm problems.

Credits

Medical text written February 2017 by Professor Colin Steward, Consultant Paediatrician, University Hospital Bristol NHS Foundation Trust, Bristol, UK.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information is provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

What are the symptoms?

The features of Barth syndrome are very variable but the majority of patients develop heart failure (cardiomyopathy) within the first year. Heart failure in young children tends to cause rapid, laboured breathing and poor feeding. Sweating with feeds is common. The heart tends to be swollen like a floppy bag (called dilated cardiomyopathy or DCM), and may have a thickened white inner lining (known as endocardial fibroelastosis or EFE) or deep pockets in the wall of one of the major pumping chambers (called left ventricular non-compaction or LVNC). Potentially serious cardiac rhythm problems may occur and there may be a previous family history of sudden death.

The blood neutrophil count varies unpredictably between low and normal but can be normal at all times in 10% of affected males. When it is very low (termed severe neutropenia), boys may develop sore red gums (complaining when their teeth are brushed), mouth ulcers, nappy rashes and bacterial infections. Muscles are weak and affected babies are often slow to sit, walk or run (called ‘delayed motor milestones’ or ‘motor delay’). They may have difficulty when rising from sitting on the floor, have a rather waddling gait on running and difficulty in kicking a football.

What are the causes?

Barth syndrome is caused by mutations in a gene called tafazzin (TAZ), which is located on the X chromosome. Although the mechanism is not clearly understood, this seems to affect the cell’s ability to produce energy, explaining weak muscles, fatigue, poor stamina and heart muscle failure.

How is it diagnosed?

Analysis of phospholipids called cardiolipins in blood or tissue samples, can be obtained via the NHS national service for the disease. Patients with abnormal cardiolipin ratios are then offered sequencing of the causative TAZ gene.

How is it treated?

Often the heart failure can be controlled by drug treatment (although boys may stabilise for a period but then deteriorate unexpectedly). Heart transplantation may be necessary if heart failure cannot be controlled.

Preventative daily antibiotics will reduce the risk of bacterial infection if boys are severely neutropenic. However, many boys require the use of a medicine called granulocyte colony stimulating factor (G-CSF), usually given three times per week, to prevent bacterial infections and improve quality of life.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Barth syndrome is inherited as an X-linked recessive trait. Detailed genetic counselling is advisable when Barth syndrome is identified in a family.

Prenatal diagnosis
Prenatal diagnosis is possible at an early stage in pregnancy in families where the mutation is known. Several blood tests taken from a mother after seven weeks of pregnancy can now identify whether she is carrying a male foetus with at least 98% certainty. This may help parents in their decision about going on to a test such as chorionic villus sampling (from 11 weeks of pregnancy onwards) or amniocentesis (from 15 weeks onwards). These tests exclude the disease by testing for the change in the TAZ gene but carry a very small risk of causing miscarriage.

Is there support?

Barth Syndrome Trust

Tel: 01794 518785
Email: via website
Website: barthsyndrome.org.uk

The Trust is a Registered Charity in England and Wales No. 1100835, established in 2003. It provides information and support to those affected by Barth syndrome and their families. The Trust aims to raise awareness of the syndrome amongst health professionals and raises funds to support research. It is involved in delivering a specialised service through the Bristol Royal Hospital for Children.

Group details last checked March 2017.

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