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The hereditary stomatocytoses: genetic disorders of the red cell membrane permeability to monovalent cations.

The hereditary stomatocytoses are mostly accounted for by genetic disorders of red cell membrane permeability to monovalent cations. These conditions, all very rare, are comprised of a hemolytic anemia, frequently macrocytosis, and the presence of abnormally shaped red blood cells. The key test for diagnosis is osmotic gradient ektacytometry, which measures the osmotic resistance and hydration of the red blood cell; the curve depicting the temperature dependence of the cation leak is also important. Syndromes include familial pseudohyperkalemia (FP), which is devoid of hematological features, dehydrated hereditary stomatocytosis (DHS), and overhydrated hereditary stomatocytosis (OHS). Some forms of DHS may be a pleiotropic, showing pseudohyperkalemia and/or perinatal edema. Perinatal edema, if not properly treated, may be lethal but may also resolve spontaneously prior to or shortly after birth and never reappear. Hereditary cryohydrocytosis, type 1 (CHC 1) is characterized by a dramatic resumption of the leak in vitro as the temperature approaches 0 degrees C; cell hydration seems unaltered. In OHS, stomatin, a membrane protein, is sharply reduced; however, this is a secondary event and the primarily mutated protein remains unknown. Hereditary cryohydrocytosis, type 2 (CHC 2) presents similar to OHS, except that the leak dramatically increases close to 0 degrees C. In addition, hematological manifestations are associated with neurological disorders. Of critical practical importance is that splenectomy in DHS or OHS causes thromboembolic events that may be fatal. The genes involved in hereditary stomatocytoses have yet to be identified. Apart from the 16q24-qter locus, related to subsets of DHS and FP, and a chromosome 2 locus assigned to a single case of FP, gene mapping has been difficult. The eventual discovery of individual genes will clarify complicated classification of the stomatocytoses, now based solely on phenotype.