Anemia, sideroblastic

X-linked sideroblastic anemia is not a porphyria but is included here because 6-aminolevulinic acid synthase is involved. 

Anderson KE et al Disorders of heme biosynthesis X-linked sideroblastic anemia and the porphyrias. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR et al (editors). McGraw-Hill, 2001. 

Pyridoxine (B ) Pyridoxal-P (PLP) Aminotransferases (transaminase) AST (GOT), ALT (GPT) 8-Aminolevulinate synthase Protein catabolism Heme synthesis MCC isoniazid therapy Sideroblastic anemia Cheilosis or stomatitis (cracking or scaling of lip borders and corners of the mouth) Convulsions... 

ALA synthase, the rate-limiting enzyme, requires pyridoxine (vitamin B ). Deficiency of pyri-doxine is associated with isoniazid therapy for tuberculosis and may cause sideroblastic anemia with ringed sideroblasts. 

Lead inactivates many enzjnnes including ALA dehydrase and ferrochelatase (hetne synthase), and can produce a microcytic sideroblastic anemia with ringed sideroblasts in the bone marrow. Other symptoms include ... 

Answer D. Sideroblastic anemia in a person being treated for tuberculosis (with isoni-azid) is most likely due to vitamin deficiency. 6-Aminolevulinate synthase, the first enzyme in heme synthesis requires vitamin Bj (pyridoxine). 

Adverse reactions may include the following Fever porphyria dysuria gout hepatic reaction nausea vomiting anorexia thrombocytopenia and sideroblastic anemia with erythroid hyperplasia vacuolation of erythrocytes increased serum iron concentration adverse effects on blood clotting mechanisms mild arthralgia and myalgia hypersensitivity reactions including rashes, urticaria, pruritus fever acne photosensitivity porphyria dysuria interstitial nephritis. 

Anemia Administration has been associated in a few cases with vitamin B-12 or folic acid deficiency, megaloblastic anemia, and sideroblastic anemia. If evidence of anemia develops, institute appropriate studies and therapy. 

Pyridoxine vitamin Bf) deficiency symptoms are generally expressed as alterations in the skin, blood, and central nervous system. Symptoms include sensory neuritis, mental depression, and convulsions. Hypochromic, sideroblastic anemia also may result. Since pyridoxine is required for the conversion of tryptophan to diphos-phopyridine and triphosphopyridine nucleotides, pellagralike symptoms can occur with vitamin Bg deficiency. This deficiency is found most often in conjunction with other B complex deficiencies. 

Different classifications of anemia are based in part on the pathophysiological factor inducing the decreased hemoglobin concentration. Anemias due to cell hy-poproliferation include aplastic anemia and iron deficiency anemia. Hemolytic anemia results from excessive destruction of red blood cells. Megaloblastic anemia, sideroblastic anemia, and iron deficiency anemia result from an abnormality in the maturation of red blood cells. 

Sideroblastic anemia is characterized by excessive iron in the cells that cannot be incorporated into porphyrin to form heme. Although it is rare, the most common cause of sideroblastic anemia is alcoholism and pyridoxine deficiency. Pyridoxine is required for the formation of pyri-doxal phosphate, a coenzyme in porphyrin synthesis. 

Pearson syndrome [24] A refractory sideroblastic anemia, with variable neutropenia and thrombocytopenia, vacuolization of marrow precursors, and exocrine pancreatic dysfunction. Severe transfusion-dependent macrocytic anemia begins in early infancy (before 1 year) and the disease is fatal before 3 years in 62% of cases. Large-scale heteroplasmic deletions/duplications of mtDNA are constantly observed in affected and nonaffected organs. 

Sideroblastic anemia j Aarskog-Scott syndrome PGK deficiency hemolytic anemia... 

Androgens also have been used in the management and treatment of agnogenic myeloid metaplasia, aplastic anemia, breast cancer, hereditary angiodema, osteoporosis, paroxysmal nocturnal hemoglobinuria, and sideroblastic anemia. 

Iron loading of mitochondria is observed in sideroblastic anemia in both animals and man (for review, see Ref. 69). The prototype of this... 

Sideroblastic anemia 8-Aminolevulinate synthase (1 heme synthesis) 2.3.1.37... 

As shown in Table 9.4, vitamin Be dependency has been reported in cases of type I primary hyperoxaluria, xanthurenic aciduria, homocystinuria, hypochromic sideroblastic anemia, gyrate atrophy with ornithinemia, and vitamin Be responsive infantile convulsions. In this last condition, the underlying defect has not been identified, but is almost certainly not impaired activity of glutamate decarboxylase. 

Pyridoxal phosphate is required for the synthesis of delta aminolevulinic acid, a precursor of heme. Vitamin B-6 deficiency occasionally cause sideroblastic anemia, which is characteristically a microcytic anemia, observed in the presence of high serum iron. 

The longer-term effects of immunosuppression, and in particular the residual hematological and immunological abnormalities in patients with aplastic anemia treated with antilymphocjde globulin, have been documented there is toxicity to hemopoietic cells, eventually leading to clonal marrow diseases years after treatment (37). Paroxysmal nocturnal hemoglobinuria, refractory sideroblastic anemia, chronic myelomonocytic leukemia, or acute leukemia can develop 4-10 years after treatment (40). 

Agranulocytosis, thrombocytopenia, hemolytic anemia, sideroblastic anemia (17), pure red cell aplasia (18), methemoglobinemia, and eosinophilia can occur exceptionally during isoniazid treatment (SEDA-9, 268) (19). An acquired coagulation factor XIII inhibitor developed in a patient taking isoniazid and resulted in a bleeding disorder (20). 

Linezolid has been associated with reversible myelosup-pression (14), which appears to be related to the duration of therapy, with a higher risk after more than 2 consecutive weeks of treatment (15). Myelosuppression with red cell hypoplasia has been reported in three patients taking linezolid 600 mg bd. The bone marrow changes were similar to those seen in reversible chloramphenicol toxicity. Another patient had sideroblastic anemia after taking linezolid for 2 months (16,17). 

Sideroblastic anemia is characterized by the accumulation of iron in the mitochondria of erythroblasts. In a Phase I study in 35 patients with refractory tumors, eight taking CMT-3 developed anemia without leukopenia or thrombocytopenia (54). Three of these patients underwent bone-marrow examination and each had ringed side-roblasts. The authors referred to several cases of aplastic anemia, megaloblastic anemia, and hemolytic anemia in which members of the tetracycline family have been implicated. However, they stated that there has been no previous reports of sideroblastic anemia associated with any tetracycline derivative and that the molecular mechanisms by which CMT-3 might cause sideroblastic anemia are unclear. 

Rudek MA, Horne M, Figg WD, Dahut W, Dyer V, Pluda JM, Reed E. Reversible sideroblastic anemia associated with the tetracychne analogue COL-3 Am J Hematol 2001 67(l) 51-3. 

There have been several cases of sideroblastic anemia, characterized by an excess of ringed sideroblasts in the bone marrow, as a suspected adverse effect of trientine (8,9). 

Zinc sulfate can cause copper deficiency by inducing the production of metaUothionein in intestinal cells and thus lowering copper absorption copper deficiency can lead in turn to sideroblastic anemia (8), neutropenia, and osteopenia (9). 

Fiske DN, McCoy HE 3rd, Kitchens CS. Zinc-induced sideroblastic anemia report of a case, review of the literature, and description of the hematologic syndrome. Am J Hematol 1994 46(2) 147-50. 

Patterson WP, Winkelmann M, Perry MC. Zinc-induced copper deficiency megamineral sideroblastic anemia. Ann Intern Med 1985 103(3) 385-6. 

The most common cause of iron overload is thalassemia, particularly in the parts of the world where it is prevalent (see earlier section). Indeed, the cardiac complications of iron overload are among the most common causes of death in I-thalassemia major. Sideroblastic anemias are a group of iron-loading disorders, many of which are of unknown cause. In a hereditary type of this disorder, there is deficiency of erythroid specific 5-aminolevulinic acid synthetase in RBC precursors because of mutations involving the X-linked gene that encodes this enzyme. Iron storage is common in patients with congenital dyserythropoietic anemia and may be found in patients with red cell enzyme deficiencies, particularly pyruvate kinase deficiency. ... 

Cazzola M, May A, Bergamaschi G, Cerani P, FerriUo S, Bishop DF. Absent phenotypic expression of X-linked sideroblastic anemia in one of two brothers with a novel ALAS2 mutation. Blood 2002 100 4236-8. 

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