ALFA TRIPTAESEMIA: Symptoms and treatment

Hereditary Alfa-Tripthasemia (Hαt) is a frequent genetic condition that raises tripty levels, an enzyme related to allergic reactions. It can cause mild or non -existent symptoms to severe anaphylaxis and digestive, neurological or cardiovascular alterations.

HαT was described in 2016. It is a disease characterized by a Increased number of copies of the TPSAB1 gene that encodes the a-tripase. The tripty in humans is encoded by 4 TPSG1, PSB2, TPSAB1 and TPSD1 genes located on chromosome 16p13.3. The disease has a dominant autosomal pattern, which means that if one of the two parents suffers, there is a 50 percent chance that a child was inherited. It affects 4-7% of the general population.

Tryptase is an enzyme produced and stored mainly by cells called mast cells, which is released in cases of IgE immunoglobulin mediated (hypersensitivity reaction type I) and in mastocyte activation syndrome (SAM). The liberation of triptase with other mediators (histamine, leukotrienes, prostaglandins …) can cause: redness (“flushing”), urticaria and angioedema (swelling of the face, lips or throat), Difficulty breathing and bronchospasmgastrointestinal problems (abdominal pain, diarrhea, nausea), dizziness or fainting due to the decrease in blood pressure or anaphylaxis (severe allergic reaction with vital risk).

Hαt symptoms

The clinical relevance of Hαt is still debated, since Many individuals do not present symptoms While others may experience paintings severe anaphylaxis. HαT symptoms often can overlap with those produced by mastocyte activation. The symptoms that patients with Hαt have the most frequently include:

• Depression, sleep and memory alterations.
• Gastrointestinal symptoms: irritable colon, nausea and reflux.
• Joint hyperlaxity.
• Autonomous system dysfunction: Orthostatic hypotension, palpitations, tachycardia, preslincope, syncope.
• Chronic pain, tiredness.
• Symptoms secondary to the release of mastocyitic mediators (“flushing”, pruritus, urticaria and anaphylaxis).

Hαt+ is associated with an increase in risk for severe allergic reactions to the hymenopter poison (an insect type), Severe idiopathic anaphylaxis and severe anaphylaxis triggered by food in children.
In some patients, Hαt+ is associated with the presence of mastocyte pathology: SAM and/or systemic mastocytosis (group of rare diseases in which mast cells accumulate in the skin or in the bone marrow, gastrointestinal tract, liver or spleen) especially with non -advanced forms of the disease.

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How is it diagnosed?

Hαt diagnosis is based on Measurement of serum tripty levels:

• The value of basal triptase (SBT) in blood is usually approximately 5 ng/ml. The upper limit of normality is considered 11.4 ng/ml.
• Hαt usually have basal triptase figures> 11.4 ng/ml; although there are cases with normal tripty values ​​(rarely <8 ng/ml).
• High SBT values ​​can be found in other pathologies such as systemic mastiffs, myeloid neoplasms, renal failure, obesity, cardiovascular disease or parasitic infections.
• Several studies have identified SBT levels as a biomarker associated with the increase in the prevalence and severity of anaphylaxis.
• It is considered an anaphylaxis marker when the value of acute serum triptase (AST) (the one obtained between 30-120 minutes of the start of the symptoms) and the basal serum tripty (SBT) (the one obtained at least 24 hours after the event) is compared and demonstrated an increase of 20% + 2 ng/ml between the two values.

Specific genetic tests to detect additional copies of the TPSAB1 gene. These genetic tests are only carried out in certain reference centers.

How is it?

It is still a very unknown disease and that currently does not have a specific treatmentwhose handling focuses on relieving the symptoms present and preventing serious allergic reactions. This may include the use of antimediating treatment that is usually used in the mastocitary pathology such as omalizumab. The use of several monoclonal antibodies that inhibit triptase or aimed at mast cell inhibitory receptors are also being studied.

What you should know …

• The alpha-hereditary tripthasemia (Hαt) is a common genetic condition (4-7% of the population) caused by an increase in the number of copies of the TPSAB1 gene, which raises the basal levels of triptase, an enzyme released by mast cells involved in allergic reactions and mastocyte activation syndrome.
• The symptoms of HαT are very variable, including from the absence of signs to severe paintings such as anaphylaxis, in addition to chronic symptoms such as neurological, gastrointestinal and cardiovascular alterations related to mastocitary activation.
• The diagnosis is based on the measurement of serum tripty levels and specific genetic tests, while the current treatment is symptomatic and preventive, with options under study to inhibit tripty or modulate the activation of mast cells.

Literature

• Beyens M, Toscano A, Ebo D, Gülen T, Sabato V. Diagnostic meaning of tryptase for suspected mast cell disorders. Diagnostics (Basel). 2023 Dec 14; 13 (24): 3662. DOI: 10.3390/DIAGNOSTICS13243662. PMID: 38132246; PMCID: PMC10742504.
• Li Jy, Ryder CB, Zhang H, Cockey SG, Hyjak E, Moscinski LC, Sagatys E, Song J. Review and Updates on Systemic Mastocytosis and Related Entities. Cancers (Basel). 2023 Nov 28; 15 (23): 5626. DOI: 10.3390/Cancers15235626. PMID: 38067330; PMCID: PMC10705510.
• Alfa Hereditary Tryptsemia (HAT), an emerging entity in anaphylaxis. Spanish Society of Allergology and Clinical Immunology (Website) (April 2024).