Ans. is 'd' i.e., X-linked recessive disorder that does not affect heterozygous famales Glucose 6-phosphate dehydrogenase (G6PD) deficiency, an X-linked disorder, is the most common enzymatic disorder of red blood cells in humans, affecting 400 million people worldwide. Clinical spectrum The clinical expression of G6PD variants encompasses a spectrum of hemolytic syndromes The four forms of symptomatic G6PD deficiency : Acute hemolytic anemia Favism Congenital nonspherocytic hemolytic anemia Neonatal hyperbilirubinemia G6PD deficiency is expressed in males carrying a variant gene that results in sufficient enzyme deficiency to lead to symptoms. Acute hemolytic anemia Almost all individuals with the most prevalent G6PD variants, G6PD A- and G6PD Mediterranean, are asymptomatic in the steady state. They have neither anemia, evidence of increased red cell destruction, nor an alteration in blood morphology,. o However sudden destruction of enzyme deficient erythrocytes can be triggered by ceain drugs or chemicals, by selected infections, and rarely by metabolic abnormalities (eg, diabetic ketoacidosis). Clinical course At two to four days after drug ingestion, there is the sudden onset of jaundice, pallor, and dark urine, with or without abdominal and back pain. This is associated with an abrupt fall in the hemoglobin concentration of 3 to 4 g/dL, during which time the peripheral blood smear reveals red cell fragments, microspherocytes, and eccentrocytes or "bite" cells. The anemia induces an appropriate stimulation of erythropoiesis, characterized by an increase in reticulocytes that is apparent within five days and is maximal at 7 to 10 days after the onset of hemolysis. Even with continued drug exposure, the acute hemolytic process ends after about one week, with ultimate reversal of the anemia. Inciting events Patients with class II or III variants develop intermittent hemolysis only after one or more of the following inciting events. Infection Oxidant drugs Chemical agents (eg, moth balls, aniline dyes, henna compounds) Diabetic ketoacidosis Ingestion of a beans Drugs and chemicals Primaquine, dapsone, and a number of other drugs can precipitate hemolysis in G6PD deficient subjects. Foods: a beans and bitter melon G6PD deficiency can also be precipitated by the the ingestion of fresh a beans (ism). Manifestation ofism begins 5-24 hrs after a bean ingestion and include headache, nausea, back pain. Congenital nonspherocytic hemolytic anemia Patients with class I G6PD variants have such severe G6PD deficiency that lifelong hemolysis occurs in the absence of infection or drug exposure. Such patients fall under the category of having congenital nonspherocytic hemolytic anemia. These G6PD variants have low in vitro activity and/or marked instability of the molecule, and most have DNA mutations at the glucose-6-phosphate or NADP binding sites. These sites are central to the function of G6PD, which oxidizes glucose-6-phosphate and reduces NADP to NADPH. It is presumed that the functional defect is so severe that the red cells cannot withstand even the normal oxidative stresses encountered in the circulation. Anemia and jaundice are often first noted in the newborn period, and the degree of hyperbilirubinemia is frequently of sufficient severity to require exchange transfusion. After infancy, hemolytic manifestations are subtle and inconstant. Most individuals have mild to moderate anemia (hemoglobin 8 to 10 g/dL) with a reticulocyte count of 10 to 15 percent. Pallor is uncommon, scleral icterus is intermittent, splenomegaly is rare, and splenectomy generally is of little benefit. Hemolysis can be exaggerated by exposure to drugs or chemicals with oxidant potential or exposure to a beans. Some drugs with relatively mild oxidant potential that are safe in patients with class II or class III G6PD variants may increase hemolysis in patients with class I variants. Neonatal hyperbilirubineinia The clinical picture of neonatal jaundice due to G6PD deficiency differs from neonatal jaundice seen in hemolytic disease of the fetus and newborn (HDFN) associated with Rh(D) incompatibility in two main respects. G6PD deficiency-related neonatal jaundice is rarely present at bih; the peak incidence of clinical onset is between days two and three. a There is more jaundice than anemia, and the anemia is rarely severe. The severity ofjaundice varies widely, from being subclinical to imposing the threat of kernicterus if not treated