Clinical Manifestations. G6PD deficiency has two common presentations. Individuals with the A– variant havenormal hemoglobin values when well, but develop an acute episode of hemolysis triggered by serious (bacterial) infection or ingestion of an oxidant drug. The RBC morphologyduring episodes of acute hemolysis is striking, appearing to have “bites” taken out of them (cookie cells). These areareas of absent hemoglobin that are produced by phagocytosis of Heinz bodies by splenic macrophages; as a result,the RBCs appear blistered. Clinically evident jaundice, darkurine resulting from bilirubin pigments, hemoglobinuriawhen hemolysis is intravascular, and decreased haptoglobinlevels are common during hemolytic episodes. Early on, thehemolysis usually exceeds the ability of the bone marrowto compensate, so the reticulocyte count may be low for 3to 4 days.
Laboratory Studies. The diagnosis of G6PD deficiency is based on decreased NADPH formation. G6PD levels during an acute, severe hemolytic episode may be normal, however, because the most deficient cells have been destroyed and reticulocytes are enriched with G6PD. Repeating the test at a later time when the patient is in a steady-state condition, testing the mothers of boys with suspected G6PD deficiency, or performing electrophoresis to identify the precise variant present aids in diagnosis.
Treatment and Prevention. The treatment of G6PD deficiency is supportive. Transfusions are indicated whensignificant cardiovascular compromise is present. Maintaining hydration and urine alkalization protects the kidneysagainst damage from precipitated free hemoglobin. Hemolysis is prevented by avoidance of known oxidants, particularly long-acting sulfonamides, nitrofurantoin, primaquine,dimercaprol, and moth balls (naphthalene). Fava beans(favism) have triggered hemolysis, particularly in patientswith the Mediterranean variant. Serious infection also is a potential precipitant of hemolysis in G6PD-deficient youngchildren.
Pyruvate kinase deficiency is much less common than G6PD deficiency and represents a clinical spectrum of disorders caused by the functional deficiency of pyruvate kinase.Some individuals have a true deficiency state, and others haveabnormal enzyme kinetics. The metabolic consequence ofpyruvate kinase deficiency is adenosine triphosphate (ATP)depletion, impairing RBC survival. Pyruvate kinase deficiency is usually an autosomal disorder, and most childrenwho are affected (and are not products of consanguinity) aredouble heterozygotes for two abnormal enzymes. Hemolysisis not aggravated by oxidant stress due to the profound reticulocytosis in this condition. Aplastic crises are potentiallylife-threatening. The spleen is the site for RBC removal inpyruvate kinase deficiency. Most patients have amelioration ofthe anemia and a reduction of transfusion requirements aftersplenectomy.
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