Abstract
Increased red blood cell count may result from primary erythrocytosis (polycythemia vera), but it is often due to secondary causes with increased erythropoietin levels. Secondary erythrocytosis may also be congenital due to different gene mutations of hemoglobin, hemoglobin stabilization proteins, EPO receptors, or oxygen sensing pathways. Von Hippel- Lindau gene mutation causes altered tissue oxygen sensation in VHL disease, usually with normal hemoglobin. Germline VHL mutations associate with classical VHL disease and represent genetic susceptibility for pheochromocytoma. VHL polymorphisms are mostly considered an innocent phenomenon. Still, some data indicate that these polymorphisms are not always harmless and can occur with prostate, renal, and colon cancer or even with isolated erythrocytosis. Seventy-eight patients referred to our department with elevated hemoglobin were screened for VHL mutations. There were no classical somatic VHL mutations. However, we found heterozygous (GA) or homozygous (AA) rs779805 VHL c.-195G>A polymorphism accompanied by erythrocytosis. These patients are Jak-2 negative, with normal or elevated EPO levels, sometimes with family accumulations and often phlebotomy needs, and in some cases with malignancies in the family. No other cause of erythrocytosis was found. We use phlebotomy regularly, and for those with cardiovascular risk factors, we recommend aspirin.
Highlights
Polycythemia vera (PV) diagnosis can be made based on WHO 2016 criteria, but the background to “simple” erythrocytosis cases is often unclear
Inherited erythrocytosis comes with isolated red blood cell increase and normal spleen size, and it is generally believed that the risk of clonal evolution does not accompany it
Von Hippel-Lindau (VHL) disease is a complex disorder in which increased oxygen demand of tissues results in a complex set of neoplastic disorders: i.e., clear cell renal carcinoma, pheochromocytoma, hemangioblastomas, pheochromocytoma, or pancreas cyst appearing well before the age of forty, and usually without erythrocytosis
Summary
Polycythemia vera (PV) diagnosis can be made based on WHO 2016 criteria, but the background to “simple” erythrocytosis cases is often unclear. Von Hippel-Lindau (VHL) disease is a complex disorder in which increased oxygen demand of tissues results in a complex set of neoplastic disorders: i.e., clear cell renal carcinoma, pheochromocytoma, hemangioblastomas, pheochromocytoma, or pancreas cyst appearing well before the age of forty, and usually without erythrocytosis. The background of this disease is genetic, caused by a series of mutations in the VHL gene, which is positioned on the short arm of chromosome 3 (3p25-26) [4,5]. The “G” allele is the major allele in the African population (allele frequency of 0.844 (https://www.ncbi.nlm.nih.gov/variation/tools/1000genomes/)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call