Presentation: Child with persistently raised baseline serum tryptase

A 12-year-old boy presents to paediatrics with a papular rash on his back, which has been present for four months. He has a history of eczema as a baby, and is found to have continued faltering growth. Repeated measurement of baseline serum tryptase is consistently raised at 29 and 35ng/ml. He has had a bone marrow aspiration for investigation of mastocytosis, but it was negative.

R436 testing should be considered where there is clinical suspicion of hereditary alpha tryptasemia, particularly in the context of negative investigation for mastocytosis and other myeloproliferative neoplasms (MPN) when there is persistently raised mast cell tryptase of 8.0ng/ml or above.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria, which contains information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details 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 about the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• For patients with suspected hereditary alpha tryptasemia, consider:
  • R436 Hereditary tryptasemia (single gene sequencing of TPSAB1).
• This test does not use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order and consent (record of discussion) forms.
• 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

References:

• Lyons JJ. ‘Hereditary alpha tryptasemia: genotyping and associated clinical features‘. Immunology and Allergy Clinics of North America 2018: volume 38, issue 3, pages 483–495. DOI: 10.1016/j.iac.2018.04.003
• Valent P, Akin C, Hartmann K and others. ‘Updated diagnostic criteria and classification of mast cell disorders: A consensus proposal‘. HemaSphere 2021: volume 5, issue 11, page e646. DOI: 10.1097/HS9.0000000000000646

For patients

• The Mast Cell Disease Society: Hereditary alpha-tryptasemia (HαT)