Presentation: Child with suspected Barth syndrome

A seven-year-old boy is admitted to the paediatric cardiology ward for assessment after presenting with a suspected infection. He has a murmur and imaging confirms dilated cardiomyopathy with apical hypertrabeculation. He is a small child who has always been considered clumsy and has struggled to learn to ride a bike or scooter, which has led to a referral to physiotherapy.

• A clinical and biochemical diagnosis of Barth syndrome can be made if:
  • the patient has a positive cardiolipin result (MLCL/CL ratio) where available (patients may also have raised urinary methylglutaconic aciduria (3MGA)); and
  • the patient is a male with cardiomyopathy as their primary clinical presentation with one or more of the following:
    • neutropenia;
    • skeletal myopathy;
    • pre-pubertal growth delay or short stature;
    • distinct facial features; and/or
    • a family history of unexplained recurrent miscarriage, stillbirth or sudden death.
• If a child has cardiomyopathy without a known cause they will be eligible for multiple genomic tests. See Child with hypertrophic cardiomyopathy or Child with syndromic cardiomyopathy for more information about testing.
• Genomic testing should be carried out in parallel with expert phenotypic assessment – for example, in an inherited cardiac conditions (ICC) clinical service or a specialist paediatric cardiomyopathy service – and with support from clinical genetics services where appropriate. Note that testing may occasionally be appropriate outside these criteria, following discussion in an ICC multidisciplinary team meeting.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• For information on the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• If eligibility criteria are met, discuss with/refer to your local ICC clinical service for genomic testing and family screening, including details of confirmation that the patient fulfils the criteria.
• If the patient fulfils diagnostic criteria as detailed in other published guidelines, but these guidelines differ to the eligibility criteria in the test directory, it is appropriate to refer to an ICC clinic for further assessment.
• The relevant test for suspected Barth syndrome is:
  • R391 Barth syndrome. This indication uses single gene sequencing to look for small variations in the TAZ gene.
• None of the tests outlined above use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion) form.
• Parental samples may be needed for interpretation of the child’s result. Parental samples can be taken alongside that of the child, and their DNA stored, or can be requested at a later date if needed.
• Most tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• GeneReviews: Barth Syndrome
• Genetic and Rare Diseases Information Center: Barth syndrome
• National Institute of Neurological Disorders and Stroke: Mitochondrial disorders
• NHS England: National Genomic Test Directory
• University Hospitals Bristol NHS Foundation Trust: NHS national Barth syndrome service

For patients

• Barth Syndrome Foundation
• Barth Syndrome UK