A team of doctors from the Bristol Royal Hospital for Children want to raise awareness of how the genetic disease, Barth Syndrome, can lead to the miscarriage and stillbirth of male fetuses, as well as early death of male babies in affected families.

The team have been funded by NHS Specialised Services since April 2010 to provide a national service for this disease which is inherited in an X-linked fashion, meaning that mothers carry the abnormal gene which causes the disease (but have no symptoms themselves) but 50% of their male babies will be affected by Barth Syndrome and 50% of their daughters will be carriers like themselves. The members include Dr Colin Steward and Drs Bev Tsai-Goodman/Rob Martin from Paediatric Haematology and Cardiology respectively at Bristol Royal Hospital for Children and Dr Ruth Newbury-Ecob from the Genetics Dept at St Michael's Hospital, Bristol.

Barth Syndrome (named after its Dutch discoverer, Dr Peter Barth) was first described in 1983 as a cause of three main problems:

  1. muscle weakness causing delayed motor milestones, proximal myopathy (particularly weakness of the muscles of the upper leg) and heart failure due to dilated cardiomyopathy (DCM)
  2. slow growth and
  3. low neutrophil count in the blood, increasing the risk of serious bacterial infections.

Previously, diagnosis of Barth Syndrome was based on an unreliable screening test on urine from boys who had all of these features. However, three years ago a new, highly reliable blood test was developed, which relies on measuring a phospholipid called cardiolipin in cell membranes. This has now been developed as a clinical service by the Barth Syndrome Service team and is finally allowing doctors to realise that the disease has been under-diagnosed.

The Barth Syndrome Service team has been suspicious that Barth Syndrome could cause fetal death ever since the grandmother of one of their patients explained how she had lost three boys late in pregnancy but given birth to three healthy girls. Modern biochemical and genetic testing allowed the doctors to confirm that the disease had caused a total of nine stillbirths, other miscarriages late in pregnancy and 14 male neonatal or infant deaths (but no losses of female fetuses or children) in six families with Barth Syndrome from England. Their findings have been published in the journal "Prenatal Diagnosis" and can be accessed here.

Dilated cardiomyopathy (where the heart becomes large and floppy) due to Barth Syndrome develops as early as 20 weeks gestation, putting many of the babies into heart failure by the third trimester. This may result in the death of the baby or fetal distress necessitating early delivery; fetal hydrops or neonatal heart failure. Neonates often develop a low blood sugar (hypoglycaemia) and lactic acidosis. All neonates with dilated cardiomyopathy should be tested for the disease by sending a blood sample to the Bristol team. Full details of testing can be obtained here. Where boys are stillborn, the best way to diagnose the disease is by analysis of cardiolipin in tissue. Once a case is suspected, sequencing of the TAZ gene which is responsible for the disease can also be performed in Bristol and then carrier testing can be offered to the wider family.

In summary:

How many deaths are due to Barth Syndrome?

Numbers are not yet clear as there are likely to be many cases still undiagnosed. However experts estimate that up to 100 families could be affected by Barth Syndrome throughout the UK. (This makes it a very rare cause of perinatal death.)

Does this affect me?

Barth Syndrome may be a possible diagnosis where a mother has had multiple losses of male babies in pregnancy, particularly if cardiomyopathy or hydrops has been detected. There may also be a family history of loss of male fetuses or baby boys running through the female side of the family.

If I think this might be relevant to me what should I do?

If you have lost multiple male babies late in pregnancy, you can discuss the possibility of Barth Syndrome with your doctor. Or contact the team at the Barth Syndrome Service in Bristol who will be happy to discuss your situation. Further details of the service and how to access testing can be found at: www.barthsyndromeservice.nhs.uk. Members of the team are very happy to answer queries from parents or health professionals who think they may have come into contact with children or families affected by this disease.