Familial pseudohyperkalaemia Chiswick: a novel congenital thermotropic variant of K and Na transport across the human red cell membrane

Abstract

Summary. Two families with inherited abnormalities in Na and K transport across the red cell membrane are described. Both presented with`pseudohyperkalaemia' as a result of loss of K from the red cells on storage at room temperature. Routine haematology was essentially normal, except for macrocytosis in one family. Studies of the temperature dependence of the passive leak to K showed a novel shoulder pattern with a minimum at 258C, a maximum at 108C, followed by a further fall. As in other cases of red cell-based pseudohyperkalaemia, the abnormal temperature dependence of this`leak' flux could be held to account for the loss of K from the cells at room temperature. These cases represent a novel variant of the temperature dependence of the passive leak of K and Na across the red cell membrane, and can be classified as a mild, non-haemolytic form of the group known as the hereditary stomatocytosis and allied disorders'.

Missense mutations in the ABCB6 transporter cause dominant familialpseudohyperkalemia

“…Eleven carriers and seven noncarriers from the FP Lille family were investigated in this study. FP Falkirk was previously described in a family of Pakistani origin [4,22]. The hematologic indices were normal, but macrocytosis was noted after 24-hr storage on ice.…”

“…In this family, cation leak measured in vitro in the presence of ouabain and bumetanide showed normal K 1 efflux at 378C, which increased greatly at 22 and 98C [3]. The subsequently reported asymptomatic cases of FP Chiswick and FP Falkirk [4] were remarkable for increased MCV. FP Lille was mapped to 2q35-q36 by genome-wide search [5].…”

A second locus mapping to 2q35–36 for familial pseudohyperkalaemia

“…seen in the normal, was obtained, which was essentially identical to that seen in FP Edinburgh. 8,9 The microsatellite study in 16q23-qter excluded the presence of a mutant gene in the 16q23-qter region (Figure 2).…”

“…This condition is linked to stomatocytosis as demonstrated in several trees, where stomatocytosis, perinatal oedema and familial pseudohyperkalaemia coexist. 5 To date, three types of pseudohyperkalaemia devoid of haematological signs have been found, based mostly on the leak -temperature dependence curve: (i) FP Edinburgh 1 and Lille (this work), in which the curve has a shallow slope, (ii) FP Chiswick and Falkirk, 9 in which the curve is shouldered and (iii) FP Cardiff, 10 in which the temperature dependence of the leak shows a 'U-shaped' profile with a minimum at 231C.…”

The perennial problem with potassium

“…11 Some kindreds with this disorder exhibit bizarre, temperature-dependent pseudohyperkalaemia. 12,13 The temperature of blood sample delivery, together with the duration of delivery, has also been identi¢ed as one of the most important factors in£uencing the incidence of non-hereditary spurious hyperkalaemia. However, this has mainly been attributed to the use of lithium-heparin (plasma) rather than plain gelseparation (serum) tubes.…”