Causes of<unk>  can be categorized into three groups: congenital<unk> , acquired clonal<unk> , and acquired reversible<unk> . All cases involve dysfunctional heme synthesis or processing. This leads to granular deposition of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell. Congenital forms often present with normocytic or microcytic anemia while acquired forms of<unk>  are often normocytic or macrocytic. * Congenital<unk>  * X-linked<unk> : This is the most common congenital cause of<unk>  and involves a defect in ALAS2, which is involved in the first step of heme synthesis. Although X-linked, approximately one third of patients are women due to skewed X-inactivation (lyonizations). * Autosomal recessive<unk>  involves mutations in the SLC25A38 gene. The function of this protein is not fully understood, but it is involved in mitochondrial transport of glycine. Glycine is a substrate for ALAS2 and necessary for heme synthesis. The autosomal recessive form is typically severe in presentation. * Genetic syndromes: Rarely,<unk>  may be part of a congenital syndrome and present with associated findings, such as ataxia, myopathy, and pancreatic insufficiency. * Acquired clonal<unk>  * Clonal<unk> s fall under the broader category of myelodysplastic syndromes (MDS). Three forms exist and include refractory anemia with ringed sideroblasts (RARS), refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T), and refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS). These anemias are associated with increased risk for leukemic evolution. * Acquired reversible<unk>  * Causes include excessive alcohol use (the most common cause of<unk> , pyridoxine deficiency (vitamin B6 is the cofactor in the first step of heme synthesis), lead poisoning and copper deficiency. Excess zinc can indirectly cause<unk>  by decreasing absorption and increasing excretion of copper. Antimicrobials that may lead to<unk>  include isoniazid (which interferes with pyridoxine metabolism), chloramphenicol (which, by inhibiting the synthesis of mitochondrial membrane protein, impairs mitochondrial respiration), cycloserine, and linezolid.
Sideroblastic anemia
Refractory anemia with ring sideroblasts
Myelophthisic anemia
Myomatous erythrocytosis syndrome
Refractory anemia with excess of blasts
Congenital hypoplastic anemia
Hereditary spherocytosis
Thiamine responsive megaloblastic anemia syndrome