Primary Familial and Congenital Polycythemia

Clinical characteristics: Primary familial and congenital polycythemia (PFCP) is characterized by isolated erythrocytosis in an individual with a normal-sized spleen and absence of disorders causing secondary erythrocytosis. Clinical manifestations relate to the erythrocytosis and can include plethora, the hyperviscosity syndrome (headache, dizziness, fatigue, lassitude, visual and auditory disturbances, paresthesia, myalgia), altered mental status caused by hypoperfusion and local hypoxia, and arterial and/or venous thromboembolic events. Although the majority of individuals with PFCP have only mild manifestations of hyperviscosity such as dizziness or headache, some affected individuals have had severe and even fatal complications including arterial hypertension, intracerebral hemorrhage, deep vein thrombosis, coronary disease, and myocardial infarction. To date 116 affected individuals from 24 families have been reported.

Diagnosis/testing: The diagnosis of PFCP is established in a proband with isolated erythrocytosis (hemoglobin and hematocrit above the normal reference range when adjusted for age and sex), normal hemoglobin oxygen affinity measured as P₅₀, erythropoietin (EPO) serum level below or in the lower normal range for laboratory-specific reference values, and a family history consistent with autosomal dominant inheritance. The diagnosis of PFCP can be confirmed in 12%-15% of individuals with these findings by detection of a heterozygous pathogenic variant in EPOR by molecular genetic testing.

Management: Treatment of manifestations: No management guidelines have been published. While the majority of individuals with PFCP require no regular treatment, some undergo phlebotomy to either treat symptoms of the hyperviscosity syndrome or to maintain the hematocrit at an almost normal level. Some patients require antihypertensive therapy. While low-dose aspirin can be considered for the prevention of thromboembolic events, no evidence of efficacy exists.

Prevention of primary manifestations: Maintain good hydration and avoid activities that potentially increase blood viscosity (e.g., mountain climbing, scuba diving, smoking). For those at increased risk for thromboembolic events: take precautions in higher-risk situations such as long-distance airline flights

Surveillance: Regular cardiology assessment including cardiac function (echocardiography) and blood pressure measurement. Life-long assessment for manifestations/severity of hyperviscosity syndrome and investigation of any suspicious clinical events such as thromboembolic complications.

Agents/circumstances to avoid: Dehydration; activities that could increase blood viscosity (mountain climbing, scuba diving, smoking)

Evaluation of relatives at risk: Presymptomatic diagnosis is warranted in relatives at risk in order to identify as early as possible those who would benefit from education about agents and circumstances to avoid including inappropriate treatments.

Genetic counseling: PFCP is inherited in an autosomal dominant manner. Each child of an individual with PFCP has a 50% chance of inheriting the EPOR pathogenic variant. Once the EPOR pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for PFCP are possible; note, however, that molecular genetic test results cannot predict disease onset or severity.