Maturation Disorders: The presence of anemia with an inappropriately low reticulocyte production index, macro- or microcytosis on smear, and abnormal red cell indices suggests a maturation disorder. Maturation disorders are divided into two categories: nuclear maturation defects, associated with macrocytosis, and cytoplasmic maturation defects, associated with microcytosis and hypochromia usually from defects in hemoglobin synthesis.Nuclear maturation defects result from vitamin B12 or folic acid deficiency, drug damage, or myelodysplasia. Cytoplasmic maturation defects result from a severe iron deficiency or abnormalities in globin or heme synthesis.Acquired abnormalities are usually associated with myelodysplasia, may lead to either a macro- or microcytic anemia, and are frequently associated with mitochondrial iron loading. In these cases, iron is taken up by the mitochondria of the developing erythroid cell but not incorporated into heme. The iron-encrusted mitochondria surround the nucleus of the erythroid cell, forming a ring. Based on the distinctive finding of so-called ringed sideroblasts on the marrow iron stain, patients are diagnosed as having a sideroblastic anemia--almost always reflecting myelodysplasia.Ceain medications, such as isoniazid, L-dopa, penicillamine, and cycloserine, interact with PLP due to a reaction with carbonyl groups. Pyridoxine should be given concurrently with isoniazid to avoid neuropathy. Vitamin B6 dependency syndromes that require pharmacologic doses of vitamin B6 arerare; they include cystathionine b-synthase deficiency, pyridoxine-responsive (primarily sideroblastic) anemias, and gyrate atrophy with chorioretinal degeneration due to decreased activity of the mitochondrial enzyme ornithine aminotransferase. In these situations, 100-200 mg/d of oral vitamin B6 is required for treatment.Ref: Harrison&;s Principles of Internal Medicine; 19th edition; Chapter 77 Anemia and Polycythemia; Page no: 398