Background

Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait characterized by multiple copies of the alpha-tryptase gene at the TPSAB1 locus. Previously described symptomatology involves multiple organ systems and anaphylaxis. The spectrum of mast cell activation symptoms is unknown, as is its association with specific genotypes.

Objective

To describe clinical, laboratory, and genetic characteristics of patients referred for the evaluation of mast cell activation–related symptoms and genotype-confirmed HαT.

Methods

We retrospectively describe clinical characteristics, baseline tryptase, and tryptase genotype in 101 patients. Patients were referred for mast cell activation–related symptoms and underwent genotyping to confirm diagnosis of HαT.

Results

Of 101 patients, 80% were female with average tryptase of 17.2 ng/mL. Tryptase was less than 11.4 ng/mL in 8.9% and greater than 20 ng/mL in 22.3% (range 6.2-51.3 ng/mL). KIT D816V mutation was negative in all subjects tested. 2α:3β was the most common genotype but did not correlate with tryptase levels. Unprovoked anaphylaxis was noted in 57% of the subjects with heterogeneous genotypes. Most common symptoms include gastrointestinal, cutaneous, psychiatric, pulmonary, cardiovascular, and neurologic. A total of 85% of patients were taking H₁- or H₂-antihistamines with partial symptom relief. Omalizumab was effective at suppressing anaphylaxis or urticaria in 94% of the patients.

Conclusion

HαT encompasses a broad range of baseline tryptase and should be considered in patients with symptoms of mast cell activation and tryptase levels greater than 6.2 ng/mL. Patients may present with complex symptomatology including cutaneous, gastrointestinal, neurologic, and psychiatric symptoms and anaphylaxis, some of which respond to omalizumab.

中文翻译：

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101 名肥大细胞激活相关症状（包括过敏反应）患者的遗传性 α-胰蛋白酶血症

背景

遗传性 α-类胰蛋白酶血症 (HαT) 是一种常染色体显性遗传性状，其特征是TPSAB1基因座上的 α-类胰蛋白酶基因有多个拷贝。先前描述的症状涉及多个器官系统和过敏反应。肥大细胞激活症状的范围未知，其与特定基因型的关联也是未知的。

客观的

描述转诊评估肥大细胞激活相关症状和基因型确认的 HαT 患者的临床、实验室和遗传特征。

方法

我们回顾性描述了 101 名患者的临床特征、基线类胰蛋白酶和类胰蛋白酶基因型。患者因肥大细胞活化相关症状而被转诊，并接受基因分型以确认 HαT 的诊断。

结果

在 101 名患者中，80% 是女性，平均类胰蛋白酶为 17.2 ng/mL。类胰蛋白酶在 8.9% 中低于 11.4 ng/mL，在 22.3% 中高于 20 ng/mL（范围 6.2-51.3 ng/mL）。KIT D816V 突变在所有测试对象中均为阴性。2α:3β 是最常见的基因型，但与类胰蛋白酶水平无关。在 57% 的具有异质基因型的受试者中注意到无端过敏反应。最常见的症状包括胃肠道、皮肤、精神、肺、心血管和神经系统。共有 85% 的患者服用 H ₁ - 或 H _{2 -}抗组胺药，症状部分缓解。在 94% 的患者中，奥马珠单抗可有效抑制过敏反应或荨麻疹。

结论

HαT 包含广泛的基线类胰蛋白酶，应在有肥大细胞活化症状且类胰蛋白酶水平大于 6.2 ng/mL 的患者中考虑。患者可能会出现复杂的症状，包括皮肤、胃肠道、神经系统和精神症状以及过敏反应，其中一些对奥马珠单抗有反应。