Youngest reported child with tryptase >20ug/L, found to have hereditary alpha tryptasemia (HAT)

Abstract

Guidelines recommend bone marrow biopsy for tryptase >20ug/L, but systemic mastocytosis (SM) is exceedingly rare in children. Hereditary alpha-tryptasemia (HAT) is caused by a duplication or triplication of the alpha-tryptase gene (TPSAB1), leading to overproduction of alpha-tryptase. HAT affects 6% of the population, with autosomal dominant inheritance. We report the youngest child with tryptase level >20ug/L, who is also the youngest child reported with HAT. Bone marrow biopsy was performed and assessed for mast cell infiltrates and KIT mutation, in addition to staining for tryptase and CD117. Serum and urine PGD2 levels were sent to rule out mast cell activation. Genetic testing was performed from a buccal swab using DNA amplification via digital droplet polymerase chain reaction for TPSAB1. A 3-month-old girl with mosaic Turner syndrome presented to her pediatrician with recurrent episodes of flushing, and gastroesophageal reflux requiring omeprazole. She was otherwise well with no features of SM. Tryptase level at 8 months was 19.8ug/L (normal <11.1ug/L), and 25.3ug/L when repeated. Complete blood count, liver, and renal function tests were normal. Bone marrow biopsy did not reveal evidence of mast cell infiltrate or KIT mutation. Immunohistochemical staining for tryptase and CD117 was negative. Serum and urine PGD2 levels were normal. Amplification of TPSAB1 revealed duplication, consistent with HAT. We propose that in the absence of convincing history of SM, children with elevated tryptase should first have HAT genetic testing prior to bone marrow biopsy, due to the rarity of childhood SM and genetic testing being less invasive.