A Novel VPS45 p.(His331Tyr) Variant Presenting With Severe Hypersplenism and Epstein-Barr Virus Reactivation: A Case Report.

Abstract

VPS45 deficiency is an ultra-rare autosomal recessive disorder causing severe congenital neutropenia, progressive bone marrow fibrosis, and multiorgan involvement. We report a 4-year-old patient with a novel homozygous VPS45 c.991C>T, p.(His331Tyr) variant, presenting with transfusion-refractory hypersplenism and horizontal nystagmus, whose course was further complicated by a laboratory-confirmed Epstein-Barr virus reactivation that subsequently resolved on repeat testing. An older sibling with the same diagnosis had died after failed hematopoietic stem cell transplantation. Management required double-dose blood product transfusion and multidisciplinary evaluation for splenectomy prior to transplantation, illustrating practical challenges in advanced disease management.