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Papers of the Week

2022 Apr 14




Hereditary alpha-tryptasemia modifies clinical phenotypes among individuals with congenital hypermobility disorders.


Vazquez M, Chovanec J, Kim J W, DiMaggio T, Milner JD, Francomano CA, Gurnett CA, Ritelli M, Colombi M, Lyons JJ
HGG Adv. 2022 Apr 14; 3(2):100094.
PMID: 35287299.


Hereditary alpha-tryptasemia (HαT) is an autosomal dominant (AD) genetic trait characterized by elevated basal serum tryptase ≥8 ng/mL, caused by increased α-tryptase-encoding copy number. HαT affects 5% to 7% of Western populations and has been associated with joint hypermobility. Hypermobility disorders are likewise frequently AD, but genetic etiologies are often elusive. Genotyping of individuals with hypermobility spectrum disorder (n = 132), hypermobile Ehlers-Danlos syndrome (n = 78), or axial skeletal abnormalities with hypermobility (n = 56) was performed. Clinical features of individuals with and without HαT were compared. When analyzing our combined cohorts, dysphagia (p = 0.007) and retained primary dentition (p = 0.0003) were significantly associated with HαT, while positive associations with anaphylaxis (p = 0.07) and pruritus (P = 0.5) did not reach significance likely due to limited sample size. Overall, HαT prevalence is not increased in individuals with hypermobility disorders, rather linked to a unique endotype, demonstrating how HαT may modify clinical presentations of complex patients.