Importance of the human erythrocyte in the diagnosis of inherited purine and pyrimidine disorders

Abstract

The intact erythrocyte has proved invaluable in the diagnosis of inherited purine and pyrimidine disorders. Not only can it be used to establish the integrity of a particular pathway where enzyme activity is undetectable in disrupted cells, the characteristic alterations in nucleotide patterns in some disorders have provided valuable insight into the mechanism by which the abnormal gene product produces disease. The severe GTP depletion associated with neurological deficits may mirror the situation in the brain, which like the erythrocyte is largely dependent on salvage to sustain its GTP levels. The ability of analogues to accumulate in erythrocytes may likewise give some clue as to the metabolic basis for the associated clinical manifestations, or the efficacy of a particular drug. In addition to their use in determining prognosis as well as providing a diagnosis, such studies have enabled demonstration of a novel route of ATP formation in human cells. The above changes may be masked if immediate processing is not possible.