Familial pseudohyperkalemia (ORPHA:90044)
Familial pseudohyperkalemia (FP) is an inherited, mild, non-hemolytic subtype of hereditary stomatocytosis that is associated with a temperature-dependent anomaly in red cell membrane permeability to potassium that leads to high in vitro potassium levels in samples stored below 37°C. FP is not associated with additional hematological abnormalities, although affected individuals may show some mild abnormalities like macrocytosis.
Epidemiology
The prevalence is unknown. Less than 15 kindreds have been reported in the literature so far (the majority being from the United Kingdom). The Arg723Gln substitution in ABCB6 leading to FP-Cardiff (a temperature-dependent pattern of cation leak previously recognized in a UK family) may affect 1/500 Europeans.
Clinical description
FP is an asymptomatic condition that presents through blood tests as unexpectedly high plasma potassium levels, after storage at or below room temperature.
Etiology
All families identified so far have mutations in the ABCB6 gene (2q36), leading to an inherited abnormality in the movement of ions across the red cell membrane, such that when the red cells are cooled they lose potassium into the plasma. Mutations in the PIEZO1 gene have been found in a kindred diagnosed as having FP but actually having dehydrated hereditary stomatocytosis (DHS; see this term), a condition that can have a similar presentation as FP due to the low number of stomatocytes.
Diagnostic methods
Diagnosis of FP may be suspected in patients with apparent hyperkalemia, but otherwise normal clinical and hematological findings, in whom pseudohyperkalemia due to other causes (cell lysis, extreme leukocytosis or thrombocythemia, or use of EDTA anticoagulant) has been excluded. The presence of red-cell based pseudohyperkalemia can be tested by taking heparinized blood, aliquoting, and storing aliquots at 37, 20 and 0°C over 24 hours. At time points, aliquots are taken and spun and the plasma potassium measured in the sample. In the 'pseudohyperkalemic' sample the plasma potassium will typically be normal at time zero, then rise with time in the samples which are stored at 20 and 0°C. In normal samples there is very little change at any temperature. The affected individuals may show mild abnormalities in the red cells (e.g. macrocytosis).
Differential diagnosis
FP needs to be differentiated from true hyperkalemia associated with reduced renal function, acidosis, the use of certain medications and rare diseases such as Addison's disease and pseudohypoaldosteronism type 2 (see these terms). Pseudohyperkalemia can also be caused by leukemic and thrombocythemic conditions, lysis during venipuncture and by the use of EDTA anticoagulant.
Genetic counseling
FP is inherited as an autosomal dominant trait. Genetic counseling may be provided to patients and their families to explain the autosomal dominant and fully penetrant nature of the disorder.
Management and treatment
No treatment is required. However, correct diagnosis is important so that needless urgent calls to hospital, and occasionally misplaced insulin/glucose and/or fludrocortisone treatment (for supposed true hyperkalemia) can be avoided. Because some FP variants show quite large abnormalities at refrigerator temperatures, affected individuals should not donate blood for transfusion.
Prognosis
The prognosis for patients is excellent. Most patients remain asymptomatic.

                            Last update: 
                            January 2015


                            - Expert reviewer(s): 
                            Dr Lesley BRUCE  - Pr Gordon STEWART