Abstract: Familial erythrocytosis type 2 (ECYT2), also known as Chuvash polycythemia, is a rare autosomal recessive disorder caused by pathogenic variants in the von Hippel–Lindau ( VHL ) gene, resulting in dysregulated oxygen sensing and increased erythropoietin (EPO) production. Pediatric cases are uncommon, but may be associated with serious thrombotic complications. We describe a 12-year-old girl who presented with intermittent headache and dizziness for 3 months, with recent worsening. Clinical examination showed conjunctival plethora and dusky extremities with normal oxygen saturation and no focal neurological deficits. Laboratory evaluation revealed marked erythrocytosis with hemoglobin 21.6 g/dL and hematocrit 66.2%, normal leukocyte and platelet counts, and markedly elevated serum EPO levels. Secondary causes of erythrocytosis were excluded. Whole exome sequencing identified a homozygous synonymous VHL variant (p.Asp143=), previously associated with erythrocytosis. Brain magnetic resonance imaging demonstrated bilateral watershed infarcts attributed to hyperviscosity. The child was managed with therapeutic phlebotomy, hydration, and antiplatelet therapy and remains clinically stable on follow-up. This report underscores the clinical significance of synonymous VHL variants and the importance of early genetic diagnosis to prevent thrombotic complications.
Venkatesh et al. (2026) studied this question.