Congenital erythrocytosis

Abstract

Summary Introduction Congenital erythrocytosis is by definition present from birth. Patients frequently present in childhood or as young adults and a family history may be present. The erythrocytosis can be primary where there is a defect in the erythroid compartment of secondary where increased erythropoietin production produced due to the defect leads to an erythrocytosis. Material and methods Primary causes include erythropoietin receptor mutations. Congenital secondary causes include mutations in the genes involved in the oxygen‐sensing pathway and haemoglobins with abnormal oxygen affinity. Investigations for the cause include an erythropoietin level, oxygen dissociation curve, haemoglobin electrophoresis and sequencing for known gene variants. Results The finding of a known or new molecular variant confirms a diagnosis of congenital erythrocytosis. A congenital erythrocytosis may be an incidental finding but nonspecific symptoms are described. Major thromboembolic events have been noted in some cases. Low‐dose aspirin and venesection are therapeutic manoeuvres which should be considered in managing these patients. Conclusions Rare individuals presenting often at a young age may have a congenital erythrocytosis. Molecular investigation may reveal a lesion. However, in the majority, currently no defect is identified.

Cardiopulmonary phenotype associated with humanPHD2mutation

“…), our findings support the idea that patients presenting with erythrocytosis secondary to oxygen sensing mutations should be monitored for cardiopulmonary abnormalities (Bento et al. ; McMullin ). This might be particularly important for those in whom venesection is being considered, or in patients likely to be exposed to hypoxia, such as through ascent to high altitude or during air travel.…”

“…Finally, our results may have important clinical implications. In combination with previous reports of pulmonary hypertension in patients with VHL and HIF2 mutations (Bushuev et al 2006;Smith et al 2006;Gale et al 2008;Bond et al 2011;Formenti et al 2011;Sarangi et al 2014), our findings support the idea that patients presenting with erythrocytosis secondary to oxygen sensing mutations should be monitored for cardiopulmonary abnormalities (Bento et al 2014;McMullin 2016). This might be particularly important for those in whom venesection is being considered, or in patients likely to be exposed to hypoxia, such as through ascent to high altitude or during air travel.…”

“…; Camps et al. ; McMullin ). The majority are loss‐of‐function mutations in VHL or EGLN1 ( PHD2 ), but gain‐of‐function mutations in the EPAS1 ( HIF2α ) gene have also been described.…”

“…To date, over 50 oxygen sensing mutations have been identified in patients with congenital erythrocytosis (Bento et al 2014;Camps et al 2016;McMullin 2016). The majority are loss-of-function mutations in VHL or EGLN1 (PHD2), but gain-of-function mutations in the EPAS1 (HIF2a) gene have also been described.…”

Direct targets of pSTAT5 signalling in erythropoiesis

“…Thus, an EPO-EpoR feedback loop re-establishes physiologically appropriate numbers of circulating mature red blood cells in response to need. Exogenous use of EPO, inherited mutations in the EpoR [1], and acquired gain-of-function mutations in JAK2 [2,3], induce supra-physiological production of red blood cells. Conversely, loss-of-function experiments have shown both EPO and EpoR are essential for the proliferation and survival of erythroid cells [4,5].…”