GNE Mutation-Related Congenital Thrombocytopenia in 2 Siblings: Case Reports and Literature Review #MMPMID41359897
Duzenli Kar Y; Sezgin Evim M; Mete UC; Ayyildiz Emecan D; Atik T; Meral Gunes A
J Pediatr Hematol Oncol 2025[Nov]; ? (?): ? PMID41359897show ga
BACKGROUND: GNE mutations are rare pathologic conditions that can cause severe thrombocytopenia and bleeding tendency from the neonatal period. The clinical presentation of patients with GNE mutations varies from mild skin and mucosal bleeding to life-threatening bleeding. CASE PRESENTATION: This study reported two siblings with hereditary thrombocytopenia. The 2 patients exhibited severe thrombocytopenia (platelet [PLT] count: <15,000/mm3) since the neonatal period and did not respond to intravenous immunoglobulin (IVIG) and steroids. The patients required PLT transfusions once every 1 to 2 weeks due to frequent bleeding incidence. Whole-exome sequencing was performed based on the preliminary diagnosis of inherited thrombocytopenia. A homozygous missense variant (c.1675G>A [p.Gly559Arg]) was detected in GNE. One sibling was unresponsive to the platelet receptor agonists eltrombopag and romiplostim. Meanwhile, the other sibling was unresponsive to eltrombopag but was responsive to romiplostim. CONCLUSION: The first-line treatment of patients with GNE mutations is PLT transfusion. However, the management of patients with severe thrombocytopenia and frequent bleeding is challenging. Thrombopoietin receptor agonists are administered to these patients to mitigate the risk of alloimmunization and PLT transfusion refractoriness. However, the observed responses may differ even in siblings carrying the same mutation. This differential response may be related to bone marrow megakaryocyte reserves and hepatocyte Aswell-Morell receptor levels.
J+Pediatr+Hematol+Oncol 2025 ; ? (?): ?
