Hemolytic anemia deficiency

The symptoms of vitamin E deficiency in animals are numerous and vary from species to species (13). Although the deficiency of the vitamin can affect different tissue types such as reproductive, gastrointestinal, vascular, neural, hepatic, and optic in a variety of species such as pigs, rats, mice, dogs, cats, chickens, turkeys, monkeys, and sheep, it is generally found that necrotizing myopathy is relatively common to most species. In humans, vitamin E deficiency can result from poor fat absorption in adults and children. Infants, especially those with low birth weights, typically have a vitamin E deficiency which can easily be corrected by supplements. This deficiency can lead to symptoms such as hemolytic anemia, reduction in red blood cell lifetimes, retinopathy, and neuromuscular disorders. 

As the above mentioned studies with high supplementation dosages exemplarily show, there is no known toxicity for phylloquinone (vitamin Kl), although allergic reactions are possible. This is NOT true for menadione (vitamin K3) that can interfere with glutathione, a natural antioxidant, resulting in oxidative stress and cell membrane damage. Injections of menadione in infants led to jaundice and hemolytic anemia and therefore should not be used for the treatment of vitamin K deficiency. 

Inherited aldolase A deficiency and pyruvate kinase deficiency in erythrocytes cause hemolytic anemia. The exercise capacity of patients with muscle phos-phofiaictokinase deficiency is low, particularly on high-carbohydrate diets. By providing an alternative lipid fuel, eg, during starvation, when blood free fatty acids and ketone bodies are increased, work capacity is improved. 

Type VII Tarul s disease Deficiency of phosphofructokinase in muscle and erythrocytes As for type V but also possibility of hemolytic anemia. 

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... 

In experimental animals, vitamin E deficiency results in resorption of femses and testicular atrophy. Dietary deficiency of vitamin E in humans is unknown, though patients with severe fat malabsorption, cystic fibrosis, and some forms of chronic fiver disease suffer deficiency because they are unable to absorb the vitamin or transport it, exhibiting nerve and muscle membrane damage. Premamre infants are born with inadequate reserves of the vitamin. Their erythrocyte membranes are abnormally fragile as a result of peroxidation, which leads to hemolytic anemia. 

The pentose phosphate pathway is operative in the RBC (it metabolizes about 5-10% of the total flux of glucose) and produces NADPH hemolytic anemia due to a deficiency of the activity of glucose-6-phosphate dehydrogenase is common. 

The RBC contains certain enzymes of nucleotide metabolism (eg, adenosine deaminase, pyrimidine nucleotidase, and adenylyl kinase) deficiencies of these enzymes are involved in some cases of hemolytic anemia. 

Deficiency of Giucose-6-Phosphate Dehydrogenase Is Frequent in Certain Areas Is an Important Cause of Hemolytic Anemia... 

Deficiency of spectrin results in hereditary spherocytosis, another important cause of hemolytic anemia. 

It is an important intracellular reductant, helping to maintain essential SH groups of enzymes in their reduced state. This role is discussed in Chapter 20, and its involvement in the hemolytic anemia caused by deficiency of glucose-6-phosphate dehydrogenase is discussed in Ghapters 20 and 52. 

Rasburicase (Elitek ) 0.2 mg/kg per day for up to 5 days 12,000/day Lower doses and abbreviated schedules may be used to decrease cost (0.05-0.1 mg/kg per day). May rarely cause nausea and vomiting. Contraindicated in patients with G6PD deficiency lead to hemolytic anemia. Rare cases of hypersensitivity and antibody formation. 

Hereditary Hemolytic Anemia Associated with Red Blood Cell Enzyme Deficiency. 14... 

Deficiencies of enzymes involved in glycolysis, the hexose monophosphate pathway, the closely related glutathione metabolism and synthesis, and nucleotide metabolism have emerged as causes of hereditary nonspherocytic hemolytic anemias (Table 1) (F10, Fll, M27). Some enzyme deficiencies, such as diphospho-glycerate mutase deficiency, lactate dehydrogenase deficiency, and NADH cy-... 

Hexokinase (Hx) deficiency in red blood cells is a rare disease in which the predominant clinical effect is chronic nonspherocytic hemolytic anemia. After the... 

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 triose phosphate isomerase (TPI) deficiency is an autosomal recessive disorder that has the most severe clinical manifestations of the erythroenzy-mopathies, including hemolytic anemia, neurological dysfunction, sudden cardiac death, and increased susceptibility to infection. Since the first description by Schneider et al. (S10), more than 25 unrelated families have been reported (Fll). Cases of decreased TPI activities associated with cat cry syndrome and pancytopenia were reported, whereas the correlation between TPI deficiency and these disorders was not clear. Although the degree of anemia is variable, most patients require blood transfusions. Neurological involvement, such as paraparesis, weakness, and hypotonia, is progressive in most cases. No specific therapy is available for the neuropathic manifestations of the disease, and most severely affected children fail to survive beyond the age of 5 years. 

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. 

Deficiency of GC-S is extremely rare only five cases from four unrelated families have been reported so far (B18, HI7, K23). This enzyme deficiency appears to be inherited as an autosomal recessive and has been clearly associated with a moderate chronic hemolytic anemia and a marked decrement of red blood cell GSH. Spinocerebellar degeneration and aminoaciduria were present in both homozygous siblings in the first family, whereas no neurologic deficit was noted in the other three families. 

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). 

Pyrimidine 5 -nucleotidase (P5N) deficiency appears to be the third most common cause of hereditary nonspherocytic hemolytic anemia after G6PD and PK deficiencies. To date, more than 42 cases have been reported worldwide (FI 1) since the first report by Valentine et al. (V4). This syndrome is characterized by hemolytic anemia, pronounced basophilic stippling of red blood cells (Fig. 6), and a... 

B3. Baronciani, L., and Beutler, E., Analysis of pyruvate kinase-deficiency mutations that produce nonspherocytic hemolytic anemia. Proc. Natl. Acad. Sci. U.S.A. 90,4324-4327 (1993). 

B9. Baronciani, L., Zanella, A., Bianchi, P Zappa, M Alfinito, E, Iolascon, A., Tannoia, N., Beutler, E., and Sirchia, G., Study of the molecular defects in glucose phosphate isomerase-deficient patients affected by chronic hemolytic anemia. Blood 88,2306-2310 (1996). 

B10. Baughan, M. A., Valentine, W. N., Paglia, D. E., Ways, P. O., Simon, E. R and DeMarsh, Q. B Hereditary hemolytic anemia associated with glucosephosphate isomerase (GPI) deficiency—A new enzyme defect of human erythrocytes. Blood 32,236-249 (1969). 

B13. Beutler, E Scott, S., Bishop, A., Margolis, N Matsumoto, F., and Kuhl, W Red cell aldolase deficiency and hemolytic anemia A new syndrome. Trans. Assoc. Am. Physicians 76,154-166 (1973). 

B15. Beutler, E., Carson, D., Dannawi, H., Forman, L., Kuhl, W., West, C., and Westwood, B., Metabolic compensation for profound erythrocyte adenylate kinase deficiency A hereditary enzyme defect without hemolytic anemia. J. Clin. Invest. 72,648-655 (1983). 

B18. Beutler, E., Moroose, R Lawrence, K., Kramer, L., Gelbart, T., and Forman, L Gamma-glu-tamylcysteine synthetase deficiency and hemolytic anemia. Blood 75,271-273 (1990). 

H17. Hirono, A., Iyori, H., Sekine,I.,Ueyama, J., Chiba, H., Kanno, H., Fujii, H and Miwa, S., Three cases of hereditary nonspherocytic hemolytic anemia associated with red blood cell glutathione deficiency. Blood 87,2071-2074 (1996). 

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