Hereditary stomatocytosis describes a number of inherited, mostly
autosomal dominant human conditions which affect the
red blood cell and create the appearance of a slit-like area of central pallor (stomatocyte) among erythrocytes on
peripheral blood smear. The erythrocytes'
cell membranes may abnormally 'leak' sodium and/or potassium ions, causing abnormalities in cell volume.[1] Hereditary stomatocytosis should be distinguished from acquired causes of stomatocytosis, including
dilantin toxicity and
alcoholism, as well as artifact from the process of preparing peripheral blood smears.[2]: 237
The two varieties of stomatocytosis classified with respect to cellular hydration status are overhydrated (hydrocytosis) and dehydrated (xerocytosis).[2]: 225–226 Hereditary xerocytosis is characterized by autosomal dominant mutations in PIEZO1, which encodes a cation channel whose mechanosensitive properties enable erythrocytes to deform as they pass through narrow capillaries by decreasing their intracellular volume.[4] More rarely, hereditary xerocytosis may be caused by mutations in KCNN4, which encodes a calcium ion-sensitive potassium channel that mediates the potassium efflux triggered by a rise in intracellular Ca2+ via activated PIEZO1 channels.[4] Hereditary xerocytosis occurs more commonly in African populations,[2][4] and it exhibits complex interactions with other hereditary alterations of red blood cells, including
sickle cell disease[4][5] and
malaria resistance.[4][6]
Osmosis leads to the red blood cell having a constant tendency to swell and burst. This tendency is countered by manipulating the flow of sodium and potassium ions. A 'pump' forces sodium out of the cell and potassium in, and this action is balanced by a process called 'the passive leak'. In overhydrated hereditary stomatocytoses, the passive leak is increased and the erythrocyte becomes swamped with salt and water. The affected erythrocytes have increased osmotic fragility.[4]Haemolytic anaemia results. For as yet unknown reasons, the cells take on the shape of a cup, with a 'mouth-shaped' (stoma) area of central pallor.
Overhydrated hereditary stomatocytosis is frequently linked to mutations in genes that encode components of the
band 3 complex, such as RHAG.[4] It is the altered band 3 protein complex which mediates the cation leaks that are characteristic of hydrocytotic hereditary stomatocytosis.[7]
Rare cases of hereditary spherocytosis can occur without cation leaks. These include cases of
phytosterolemia nonleaky stomatocytosis, a disorder of lipid metabolism associated with mutations in ABCG5 and/or ABCG8, which encode
sterol transporters.[1] The resulting abnormal sterol composition of erythrocyte
cell membranes causes them to appear as deformed stomatocytes on peripheral blood smear.[1]
Diagnosis
Ektacytometry may be helpful in distinguishing different subtypes of hereditary stomatocytosis.[4]
Variants
Haematologists have identified a number of variants. These can be classified as below.
At present there is no specific treatment. Many patients with hemolytic anemia take
folic acid (vitamin B9) since the greater turnover of cells consumes this vitamin. During crises transfusion may be required. Clotting problems can occur for which anticoagulation may be needed. Unlike
hereditary spherocytosis,
splenectomy is contraindicated.[11]
^Bruce LJ, Robinson HC, Guizouarn H, Borgese F, Harrison P, King MJ, et al. (November 2005). "Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1". Nature Genetics. 37 (11): 1258–1263.
doi:
10.1038/ng1656.
PMID16227998.
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^Oski FA, Naiman JL, Blum SF, Zarkowsky HS, Whaun J, Shohet SB, et al. (April 1969). "Congenital hemolytic anemia with high-sodium, low-potassium red cells. Studies of three generations of a family with a new variant". The New England Journal of Medicine. 280 (17): 909–916.
doi:
10.1056/NEJM196904242801701.
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^Thrall MA, Baker DC (2006). Veterinary Hematology and Clinical Chemistry. Blackwell Publishing. pp. 71–72.
ISBN978-0-7817-5799-7.
OCLC954019258.
Eber SW, Lande WM, Iarocci TA, Mentzer WC, Höhn P, Wiley JS, Schröter W (July 1989). "Hereditary stomatocytosis: consistent association with an integral membrane protein deficiency". British Journal of Haematology. 72 (3): 452–455.
doi:
10.1111/j.1365-2141.1989.tb07731.x.
PMID2765409.
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Hiebl-Dirschmied CM, Adolf GR, Prohaska R (June 1991). "Isolation and partial characterization of the human erythrocyte band 7 integral membrane protein". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1065 (2): 195–202.
doi:
10.1016/0005-2736(91)90230-6.
PMID1711899.
Hiebl-Dirschmied CM, Entler B, Glotzmann C, Maurer-Fogy I, Stratowa C, Prohaska R (August 1991). "Cloning and nucleotide sequence of cDNA encoding human erythrocyte band 7 integral membrane protein". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1090 (1): 123–124.
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10.1016/0167-4781(91)90047-P.
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