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 and 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, they will be eligible for multiple genomic tests. See Child with hypertrophic 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 containing details of all available tests.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• If the relevant eligibility criteria are met, discuss the case with or refer it to your local ICC clinical service for genomic testing and family screening. You will need to provide details confirming that the patient fulfils the criteria.
• If the patient fulfils diagnostic criteria as detailed in published guidelines that differ from the eligibility criteria in the test directory, it is appropriate to refer the case 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.
• Because this test does not use whole genome sequencing, you will need to:
  • complete a test order form and a consent (record of discussion) form, which are available from your local Genomic Laboratory Hub; and
  • include details of the phenotype in the test order form (using human phenotype ontology (HPO) terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
• This test is DNA based, and an EDTA sample (purple-topped tube) is required.
• 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

• Genetic and Rare Diseases Information Center: Barth syndrome
• National Institute of Neurological Disorders and Stroke: Barth syndrome
• 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