Biallelic GNE variants in patients with congenital thrombocytopenia

Abstract

Introduction Congenital thrombocytopenia can be associated not only with a reduced production, but also with an accelerated degradation of platelets. Sialic acid binds to platelet surface glycoproteins and is known to protect platelets from degradation via the Ashwell-Morell receptor. The GNE gene encodes an enzyme that initiates and regulates the biosynthesis of N-acetylneuraminic acid, a precursor of sialic acids. GNE mutations are autosomal recessive associated with adult-onset progressive GNE myopathy (with or without thrombocytopenia) and autosomal dominant with sialuria. Interestingly, so far only a few children (n<10) with biallelic GNE variants leading to isolated thrombocytopenia have been described. Recently, we identified compound heterozygous GNE variants in a young girl suffering from severe congenital thrombocytopenia. We showed decreased α2,3 sialic acid and increased terminal galactose and α2,6 sialic acid moieties of the girl´s platelets [1]. In the current study, we aimed to characterize the platelet defect in a family with two children (P1 and P2) affected by congenital thrombocytopenia. P1 is a newborn boy with thrombocytopenia since birth (lowest platelet count 6 x109/L) who needs weekly platelet transfusions. His 16-year-old sister (P2) presented with lifelong thrombocytopenia and suspected chronic immune thrombocytopenia. She received therapy with romiplostim which resulted in stable platelet counts (> 50 x109/L). The parents and two other siblings were clinically not affected.