Hemolysis deficiency

Glucose- 6-phosphate dehydrogenase Low or absent enzyme activity in about 10% of African populations. Hemolysis following intake of a number of drugs which have electrophilic reactive metabolites, but also, carriers of this enzyme deficiency have a partial protection from malaria. 

Genetic deficiency of glucose-6-phosphate dehydrogenase, with consequent impairment of the generation of NADPH, is common in populations of Mediterranean and Afro-Caribbean origin. The defect is manifested as red cell hemolysis (hemolytic anemia) when susceptible individuals are subjected to oxidants, such as the an-timalarial primaquine, aspirin, or sulfonamides or when... 

Current NKF guidelines define anemia as a hemoglobin (Hgb) level less than 11 g/dL (6.8 mmol/L).31 A number of factors can contribute to the development of anemia, including deficiencies in vitamin B12 or folate, hemolysis, bleeding, or bone marrow suppression. Many of these can be detected by alterations in RBC indices, which should be included in the evaluation for anemia. A complete blood cell count is also helpful in evaluating anemia to determine overall bone marrow function. 

On the other hand, a deficiency of aldolase A is a rare cause of hereditary hemolytic anemia. Only three families with aldolase A deficiency have been reported. In the first case, hereditary nonspherocytic hemolytic anemia, many dysmorphic features and mental and growth retardation were observed (B13). The second family had only hemolysis but no signs of myopathy (M24). The third case had both hemolytic anemia and predominantly myopathic symptoms (K25). 

Hereditary deficiency of phosphoglycerate kinase (PGK) is associated with hereditary hemolytic anemia and often with central nervous system dysfunction and/or myopathy. The first case, reported by Kraus et al. (K24), is a heterozygous female, and the results are not so clear. The second family, reported by Valentine et al. (V3), is a large Chinese family, whose pedigree study indicates that PGK deficiency is compatible with X-linked inheritance. To date, 22 families have been reported (04, T25, Y3). Nine of these have manifested both symptoms five have shown only hemolysis seven have shown the central nervous system dysfunction and/or myopathy but without hemolysis and one case, PGK Munchen, is without clinical symptoms (F5). PGK II is an electrophoretic variant found in New Guinea populations (Y2). Red blood cell enzyme activity, specific activity, and the kinetic properties of this polymorphic variant are normal. 

Necheles et al. (N4) first reported a genetically determined homozygous GSH-Px deficiency associated with neonatal jaundice and mild hemolysis. Spontaneous recovery from hemolysis was noted 3 months after birth. Thereafter, several cases with GSH-Px deficiency were reported. Newborn infants exhibit significantly lower red blood cell GSH-Px activity and serum selenium concentrations than adult control subjects, and a significantly positive correlation between selenium concentration and GSH-Px activity has been observed. Furthermore, the addition of selenium stimulates, both in vivo and in vitro, the GSH-Px activity. The neonatal red blood cell GSH-Px deficiency may be partially due to insufficient availability of selenium during pregnancy (P9). Therefore, the diagnosis of GSH-Px deficiency in newborn infants must be made carefully. 

GSH-S deficiency is a more frequent cause of GSH deficiency (HI7), and more than 20 families with this enzyme deficiency have been reported since the first report by Oort et al. (05). There are two distinct types of GSH-S deficiency with different clinical pictures. In the red blood cell type, the enzyme defect is limited to red blood cells and the only clinical presentation is mild hemolysis. In the generalized type, the deficiency is also found in tissues other than red blood cells, and the patients show not only chronic hemolytic anemia but also metabolic acidosis with marked 5-oxoprolinuria and neurologic manifestations including mental retardation. The precise mechanism of these two different phenotypes remains to be elucidated, because the existence of tissue-specific isozymes is not clear. Seven mutations at the GSH-S locus on six alleles—four missense mutations, two deletions, and one splice site mutation—have been identified (S14). 

The answers are 484-k 485-j. (tlardman, pp 1061-1062, 1682-1685.) Sulfonamides can cause acute hemolytic anemia. In some patients it mayr be related to a sensitization phenomenon, and in other patients the hemolysis is due to a glucose-6-phosphate dehydrogenase deficiency Sulfamethoxazole alone or in combination with trimethoprim is used to treat UTls. The sulfonamide sulfasalazine is employed in the treatment of ulcerative colitis. Daps one, a drug that is used in the treatment of leprosy, and primaquine, an anti mala rial agent, can produce hemolysis, particularly in patients with a glucose-6-phosphate dehydrogenase deficiency. 

Clinical consequence hemolysis (breakdown of circulating red blood cells) from antimalarials, sulfonamides, nitrofurantoin, and other drugs. a-1 Antitrypsin deficiency, due to variants in this circulating plasma protein Frequency 1 /3000 Northern European Caucasians Clinical consequence predisposition to emphysema in early middle age, especially in cigarette smokers, due to failure to protect against trypsinlike enzymes in lung... 

Decreasing G-6-PDH activity in aging erythrocytes has been described (L4, L8). This finding becomes important in hereditary G-6-PDH deficiency, explaining the self-limiting effect of drug-induced hemolysis (B9, BIO, Bll). 

It prevents peroxidation of fatty adds in cell membranes, helping to maintain their normal fluidity. Deficiency can lead to hemolysis, neurologic problems, and retinitis pigmentosa. 

In a fatal human exposure, a worker engaged in emptying metal gas cylinders of methyl mercaptan was found comatose at the work site he developed expiratory wheezes, elevated blood pressure, tachycardia, and marked rigidity of extremities. Methemoglobinemia and severe hemolytic anemia developed with hematuria and proteinuria but were brief in duration deep coma persisted until death due to pulmonary embolus 28 days after exposure. It was determined that the individual was deficient in erythrocyte glucose-6-phosphate dehydrogenase, which was the likely cause of the hemolysis and formation of methemoglobin. 

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