Hereditary Stomatocytosis

Hereditary stomatocytosis is a group of rare red cell membrane cation permeability disorders (dehydrated, overhydrated, cryohydrocytosis).

• Dehydrated hereditary stomatocytosis (xerocytosis, 90%): PIEZO1 gain of function mutations (autosomal dominant), KCNN4 (Gardos channel); red cells dehydrated and dense, MCV mildly raised, MCHC high.
• Overhydrated stomatocytosis: RHAG, SLC4A1; cells swollen, severe haemolysis.
• Phytosterolaemia mimics stomatocytosis.
• Complications: iron overload (disproportionate to transfusion), perinatal oedema or ascites (PIEZO1), pseudohyperkalaemia, thrombosis post splenectomy.

• Mild to moderate haemolytic anaemia, jaundice, splenomegaly, gallstones.
• Perinatal oedema, ascites, hydrops in dehydrated form; pseudohyperkalaemia (potassium leak from cooled samples).
• Iron overload with hepatic and cardiac complications.

• Macrocytosis (MCV 100 to 120 fL), high MCHC, few stomatocytes (under 10 to 20% in xerocytosis), reticulocytosis.
• Osmotic gradient ektacytometry (left shifted curve in xerocytosis), osmotic fragility decreased.
• Genetic testing (PIEZO1, KCNN4, RHAG, SLC4A1, ABCG5/8 for phytosterolaemia).
• Elevated ferritin, liver MRI iron quantification.
• Exclude hereditary spherocytosis, thalassaemia, liver disease, alcohol.

• Splenectomy is contraindicated or relatively contraindicated in dehydrated stomatocytosis because of high risk of thrombosis (pulmonary hypertension, portal vein thrombosis) without clear benefit.
• Supportive care: folic acid, transfusion for severe anaemia.
• Iron overload: monitor with MRI; chelation (deferasirox 20 to 30 mg/kg daily) or phlebotomy as tolerated.
• Overhydrated type: splenectomy may be considered.
• Phytosterolaemia: dietary restriction, ezetimibe 10 mg daily.
• Avoid unnecessary cooling of samples (use fresh samples for potassium).
• Perinatal ascites: supportive.
• Genetic counselling, family screening.