The diagnosis is generally suspected when patients from certain ethnic groups (see epidemiology) develop anemia, jaundice and symptoms of hemolysis after challenges from any of the above causes, especially when there is a positive family history. Generally, tests will include: * Complete blood count and reticulocyte count; in active<unk>  deficiency, Heinz bodies can be seen in red blood cells on a blood film; * Liver enzymes (to exclude other causes of jaundice); * Lactate dehydrogenase (elevated in hemolysis and a marker of hemolytic severity) * Haptoglobin (decreased in hemolysis); * A "direct antiglobulin test" (Coombs' test) – this should be negative, as hemolysis in<unk>  is not immune-mediated; When there are sufficient grounds to suspect<unk> , a direct test for<unk>  is the "Beutler fluorescent spot test", which has largely replaced an older test (the Motulsky dye-decolouration test). Other possibilities are direct DNA testing and/or sequencing of the<unk>  gene. The Beutler fluorescent spot test is a rapid and inexpensive test that visually identifies NADPH produced by<unk>  under ultraviolet light. When the blood spot does not fluoresce, the test is positive; it can be falsely negative in patients who are actively hemolysing. It can therefore only be done 2–3 weeks after a hemolytic episode. When a macrophage in the spleen identifies a RBC with a Heinz body, it removes the precipitate and a small piece of the membrane, leading to characteristic "bite cells". However, if a large number of Heinz bodies are produced, as in the case of<unk>  deficiency, some Heinz bodies will nonetheless be visible when viewing RBCs that have been stained with crystal violet. This easy and inexpensive test can lead to an initial presumption of<unk>  deficiency, which can be confirmed with the other tests. Testing during and for many weeks after a haemolytic episode will lead to false negative results as the<unk>  deficient RBC will have been excreted and the young RBC (reticulocytes)will not yet be<unk>  deficient. False negative results will also be likely following any blood transfusions. For this reason, many hospitals wait for 3 months after a haemolytic episode before testing for<unk>  deficiency. Females should have their<unk>  activity measured by quantitative assay to avoid being misclassified by screening tests. Classification The World Health Organization classifies<unk>  genetic variants into five classes, the first three of which are deficiency states. * Class I: Severe deficiency (<10% activity) with chronic (nonspherocytic) hemolytic anemia * Class II: Severe deficiency (<10% activity), with intermittent hemolysis * Class III: Moderate deficiency (10-60% activity), hemolysis with stressors only * Class IV: Non-deficient variant, no clinical sequelae * Class V: Increased enzyme activity, no clinical sequelae Differential diagnosis<unk> -phosphogluconate dehydrogenase <unk> PGD) deficiency has similar symptoms and is often mistaken for<unk>  deficiency, as the affected enzyme is within the same pathway, however these diseases are not linked and can be found within the same person.
Glucose-6-phosphate dehydrogenase deficiency
Pyruvate kinase deficiency
Ribose-5-phosphate isomerase deficiency
Hereditary spherocytosis
Glutaminase deficiency
Sickle cell disease
6-phosphogluconate dehydrogenase deficiency
Aldolase A deficiency