Aldolase A deficiency is an autosomal recessive disorder associated with hereditary hemolytic anemia (Kishi et al., 1987).

A deficiency of pyrimidine 5-prime nucleotidase (P5N), also called uridine 5-prime monophosphate hydrolase (UMPH1), causes congenital nonspherocytic hemolytic anemia-8 (CNSHA8), which is characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. The enzyme is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties. Hirono et al. (1988) suggested that this deficiency is the third most common RBC enzymopathy--after G6PD (300908) and pyruvate kinase (see 266200) deficiencies--causing hemolysis (summary by Marinaki et al., 2001).

Congenital nonspherocytic hemolytic anemia-1 (CNSHA1), caused by mutation in the G6PD gene, is the most common genetic form of chronic and drug-, food-, or infection-induced hemolytic anemia. G6PD catalyzes the first reaction in the pentose phosphate pathway, which is the only NADPH-generation process in mature red cells; therefore, defense against oxidative damage is dependent on G6PD. Most G6PD-deficient patients are asymptomatic throughout their life, but G6PD deficiency can be life-threatening. The most common clinical manifestations of G6PD deficiency are neonatal jaundice and acute hemolytic anemia, which in most patients is triggered by an exogenous agent, e.g., primaquine or fava beans. Acute hemolysis is characterized by fatigue, back pain, anemia, and jaundice. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. The striking similarity between the areas where G6PD deficiency is common and Plasmodium falciparum malaria (see 611162) is endemic provided evidence that G6PD deficiency confers resistance against malaria (summary by Cappellini and Fiorelli, 2008).