Hereditary alpha-tryptasaemia

Hereditary alpha-tryptasaemia is a genetic condition in which a person has extra copies of the gene coding for tryptase, an enzyme released by certain immune cells, resulting in persistently elevated baseline tryptase levels in the blood. It can be associated with a range of symptoms, though some people with the genetic trait have few or no symptoms at all. It has only relatively recently been well characterised as a distinct genetic condition.

It is caused by having extra copies (duplications) of the TPSAB1 gene, which codes for alpha-tryptase, inherited in an autosomal dominant pattern, meaning a single altered gene copy from one parent is enough to be affected. The number of extra gene copies someone has can influence how high their tryptase level is and, to some extent, symptom severity. It is a relatively common genetic trait, though not everyone who carries it experiences significant symptoms.

Symptoms can be highly variable and include flushing, itching, abdominal symptoms, joint and connective tissue symptoms, and, in some people, more significant allergic-type reactions or symptoms overlapping with conditions like mast cell activation syndrome. Some people with the genetic trait have no symptoms at all and are only identified because of an incidentally elevated tryptase level found during other testing. The reasons for this wide variability in symptom presence and severity are still being researched.

For many people, it does not cause significant health problems and is simply a genetic trait associated with a higher baseline tryptase level. In some people, it is associated with more troublesome symptoms or an increased severity of allergic reactions, including to insect stings, which is an important consideration for those affected. An allergy or immunology specialist can help assess individual risk and any need for specific precautions.

Yes, it is a genetic condition caused by inherited gene duplications, following an autosomal dominant pattern, meaning each child of an affected parent has a 50% chance of inheriting it. Genetic testing can confirm the diagnosis and the specific number of gene copies present. Family members of someone diagnosed may wish to consider testing, particularly if they have relevant symptoms.

Management depends on the individual’s specific symptoms, ranging from no specific treatment needed for asymptomatic carriers, to symptom-targeted treatment such as antihistamines for those with allergic-type symptoms. People with a history of severe allergic reactions, particularly to insect stings, may be advised to carry emergency adrenaline auto-injectors and undergo specific allergy assessment. An allergist or immunologist experienced with this relatively newly characterised condition can tailor an individual management plan.

There is no cure for the underlying genetic trait itself, since it reflects a fixed genetic difference present from birth. However, associated symptoms, where present, can often be effectively managed with appropriate treatment tailored to the individual’s specific symptom pattern. Most people with this condition can lead entirely normal lives with appropriate understanding and, where needed, symptom management.

Hereditary alpha-tryptasaemia is a genetic trait causing elevated baseline tryptase due to extra gene copies, without necessarily involving abnormal mast cell proliferation. Mastocytosis is a separate condition involving an actual increase in the number of mast cells within tissues, which can also raise tryptase levels but through a different underlying mechanism. The two conditions can sometimes coexist, and specific testing, including genetic testing and sometimes bone marrow examination, helps distinguish between them when needed. An allergist or haematologist can clarify which condition, or combination, applies to an individual’s specific test results.

See an allergy or immunology specialist if you have an incidentally found elevated tryptase level, relevant symptoms such as unexplained flushing or severe allergic reactions, or a family history of this condition. A private allergy and immunology assessment can typically be arranged within about one to two weeks. Genetic testing can help confirm the diagnosis and, where relevant, guide specific precautions such as carrying emergency allergy treatment.