Clinical Guidance

No clinically relevant genotype-phenotype correlations have been identified.

Source: GeneReviews — "Primary Familial and Congenital Erythrocytosis"

Penetrance

Penetrance is reduced, but data are insufficient to determine penetrance for EPOR-related PFCE.

Source: GeneReviews — "Primary Familial and Congenital Erythrocytosis"

Diagnostic Criteria

Consensus clinical diagnostic criteria for primary familial and congenital erythrocytosis (PFCE) – originally described as primary familial and congenital polycythemia – have been published .

Suggestive Findings

PFCE should be suspected in individuals with the following clinical and laboratory findings and family history.

Clinical findings

• Absence of marked splenomegaly

• Absence of cardiac, pulmonary, and kidney disease causing secondary erythrocytosis

• Rubor

Laboratory findings

Source: GeneReviews — "Primary Familial and Congenital Erythrocytosis"

Differential Diagnosis

Causes of erythrocytosis to be considered in the differential diagnosis of primary familial and congenital erythrocytosis (PFCE) include acquired primary erythrocytosis and secondary erythrocytosis.

• Primary erythrocytosis/polycythemia refers to erythrocytosis caused by intrinsic abnormalities of erythroid progenitors that renders them hypersensitive to erythropoietin (EPO) stimulation or EPO independent and associated with decreased EPO. In acquired primary erythrocytosis (polycythemia vera), erythrocytosis is caused by a somatic JAK2 gain-of-function pathogenic variant.

• Secondary

erythrocytosis refers to erythrocytosis caused by circulating stimulators of erythroid progenitors. Secondary erythrocytosis can be acquired or inherited and can result from:

Source: GeneReviews — "Primary Familial and Congenital Erythrocytosis"

Management Guidelines

No clinical practice guidelines for primary familial and congenital erythrocytosis (PFCE) – originally described as primary familial and congenital polycythemia – have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with PFCE, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

Primary Familial and Congenital Erythrocytosis: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Hematologic

| Full blood count |

Hyperviscosity syndrome

| Assess document symptoms severity of hyperviscosity syndrome:Symptoms:

• Headache

• Dizziness

• Altered mentation

• Visual disturbances

• Tinnitus

• Paresthesia

• Low performance

• Fatigue, lassitude

• Muscle weakness

| Severity:

• Grade 1. Mild; does not interfere w/normal activities

• Grade 2. Moderate; interferes w/some activities

• Grade 3. Marked to severe; interferes w/most or all activities

Cardiac

| • Eval w/cardiologist

• Blood pressure measurement

• Echocardiography

| In those w/ blood pressure, perform 24-hour blood pressure assessment.

Genetic counseling

| By genetics professionals1 | To obtain a pedigree inform affected persons their families re nature, MOI, implications of PFCE to facilitate medical personal decision making

Source: GeneReviews — "Primary Familial and Congenital Erythrocytosis"

Clinical Guidance

Avoid the following:

• Dehydration

• Any activity that would potentially increase blood viscosity (e.g., living or prolonged stay at high altitudes, scuba diving, and smoking)

• Additional cardiovascular risks if possible (e.g., hypertension, hyperlipidemia, diabetes, and obesity)

• Erythropoesis-stimulating agents

Source: GeneReviews — "Primary Familial and Congenital Erythrocytosis"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Primary Familial and Congenital Erythrocytosis"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 5.

Primary Familial and Congenital Erythrocytosis: Recommended Surveillance

System/Concern | Evaluation | Frequency

Hematologic

| Full blood count | As needed (e.g., w/onset of new symptoms)

Hyperviscosity syndrome

| Assess document symptoms severity of hyperviscosity syndrome:Symptoms:

• Headache

• Dizziness

• Altered mentation

• Visual disturbances

• Tinnitus

• Paresthesia

• Low performance

• Fatigue, lassitude

• Muscle weakness

Severity:

• Grade 1. Mild; does not interfere w/normal activities

• Grade 2. Moderate; interferes w/some activities

• Grade 3. Marked to severe; interferes w/most or all activities

| At each visit or as needed

Cardiac

| • Cardiology assessment

• Blood pressure measurement

• Echocardiography

• Plasma lipid panel

• Hgb A1c

• In those w/ blood pressure, perform 24-hour blood pressure assessment.

| Every few years or as recommended by cardiologist

Thromboembolic events

| Assess for any clinical manifestations suspicious for thromboembolic event. | At each visit or as needed

Source: GeneReviews — "Primary Familial and Congenital Erythrocytosis"