Endocrine Abstracts

Hereditary stomatocytoses, including cryohydrocytosis, are anaemias in which the erythrocyte membrane has increased permeability resulting in electrolyte leakage and thus haemolysis. Many forms and underlying molecular mechanisms exist. GLUT1 is present in the blood–brain barrier and erythrocytes, but GLUT1-deficiency does not usually affect erythrocytes. We describe a child with a stomatocytosis due to a SLC2A1 mutation presenting with hyperkalaemia, liver disease, microcephaly, nystagmus, and seizures.

The patient presented aged 1 day with jaundice and hypoglycaemia, and was treated for presumed sepsis. Plasma K⁺-concentration was reported to be >8 mmol/l. The child continued to have conjugated hyperbilirubinaemia; a liver biopsy suggested non-specific hepatitis. She developed abnormal movements, nystagmus and microcephaly; EEG was normal but MRI showed periventricular calcifications. Aged 4 months, she developed seizures and was developmentally delayed. Hyperkalaemia continued, requiring occasional treatment with Salbutamol, Insulin or Fludrocortisone. Adrenal pathology was excluded. Investigation suggested normokalaemia when samples were assayed immediately and therefore ‘pseudo-hyperkalaemia’. Continuing hyperbilirubinaemia and occasional splenomegaly lead to a suspicion of a ‘leaky erythrocytes’. Incubation of blood at 37, 20 and 0 °C, showed increasing extracellular K⁺-concentration and decreasing intracellular K⁺-concentration with reducing temperature, and deranged intracellular Na⁺/ K⁺-concentration in fresh erythrocytes, suggesting ‘stomatin-deficient cryohydrocytosis’. Indeed, a blood film showed erythrocyte fragments. Glucose-concentration in CSF was 2.0 mmol/l (plasma 3.8 mmol/l), consistent with reduced glucose transport across the blood–brain barrier. Direct sequencing of SLC2A1 revealed a de novo heterozygous ATC deletion (p.Ile435or436del). This SLC2A1-mutation has been found previously in an adult with stomatin-deficient cryohydrocytosis but this is the first paediatric presentation described. The mutation both prevents glucose transport and causes a cation leak. A ketogenic diet improved seizures and reduced abnormal movements, as in the more common GLUT1-deficiency syndrome. In conclusion, pseudohyperkalaemia needs to be considered in assessment of hyperkalaemia. GLUT1-deficient cryohydrocytosis may present with haemolytic anaemia, pseudohyperkalaemia and neuro-pathology.