“The unique fusion of individual innovative technologies will provide a novel diagnostic tool leading to a better understanding of the underlying pathophysiology of rare anaemia.”

Lars Kaestner, Coordinator of CoMMiTMenT

Rare anaemias

The current candidate RA that are targeted by CoMMiTMenT are hereditary xerocytosis, overhydrated hereditary stomatocytosis, familial pseudohyperkalaemia, cryohydrocytosis, certain types of spherocytosis, hyperphosphatidylcholine haemolytic anaemia, sickle cell anaemia, thalassemia syndromes, and RBC enzymopathies (i.e., disorders of glycolysis and glutathione metabolism), especially those that are associated with mental retardation and/or neurological disease. An overview on anaemias is provided by ENERCA.

Recent studies indicate that several RA are associated with altered cellular ion homeostasis. There are scenarios in which RA may be due to structural RBC abnormalities due to congenital membrane protein defects and glucose transporter GLUT1 mutations, which cause paroxysmal exertion-induced dyskinesias, inducing haemolytic anaemia by a cation leak. A third category of RA associated with altered cellular ion homeostasis is enzyme deficiency (e.g., phosphofructokinase deficiency). Moreover, it appears reasonable to assume that novel, unidentified ion homeostasis disturbances may significantly contribute to anaemia pathophysiology and may constitute an important group of undiagnosed cases of RA.

There is an increasing amount of evidence that disturbances of RBC ion homeostasis are the result of altered ion channel function. This group of so-called channelopathies is a heterogeneous group of diseases of which the molecular basis is, at large, unknown. Therefore, there are few or no treatments for patients who are affected by these disorders. Interestingly, several hereditary haemolytic anaemia are also associated with neurological diseases, many of which are known to be caused by channelopathies. However, this apparent relationship between the disorders remains unexplored.