Other Glycolytic Enzyme Abnormalities All of these defects are rare to very rare (Table 96-4), and most of them cause HA with varying degrees of severity. It is not unusual for the presentation to be in the guise of severe neonatal jaundice, which may require exchange transfusion; if the anemia is less severe, it may present later in life, or it may even remain asymptomatic and be detected incidentally when a blood count is done for unrelated reasons. The spleen is often enlarged. When other systemic manifestations occur, they can involve the central nervous system (sometimes entailing severe mental retardation, particularly in the case of triose phosphate isomerase deficiency), the neuromuscular system, or both (see Table 96-4). This is not altogether surprising, if we consider that these are housekeeping genes, i.e., expressed in all tissues. The diagnosis of HA is usually not difficult, thanks to the triad of normomacrocytic anemia, reticulocytosis, and hyperbilirubinemia. Enzymopathies should be considered in the differential diagnosis of any chronic Coombs-negative HA. Unlike with membrane disorders, in most cases of glycolytic enzymopathies morphologic abnormalities are conspicuous by their absence. A definitive diagnosis can be made only by demonstrating the deficiency of an individual enzyme by quantitative assays; these are carried out in only a few specialized laboratories. If a particular molecular abnormality is already known in the family, then one could test directly for that defect at the DNA level, thus bypassing the need for enzyme assays. Of course the time may be getting nearer when a patient will present with her or his exome already sequenced, and we will need to concentrate on which genes to look up within the file. The principles for the management of these conditions are similar as for PK deficiency. In isolated cases of glycolytic enzyme abnormalities BMT has been carried out successfully: although unfortunately non-hematologic manifestations, if any, are not reversed.