Causes of reversible acquired sideroblastic anemia
| Alcohol abuse | Alcohol and its metabolite, acetaldehyde, can inhibit several steps of the heme synthetic pathway. Mitochondrial iron accumulation seems to reflect an imbalance between the large amounts of iron imported into mitochondria for heme synthesis, and insufficient production of protoporphyrin IX to incorporate the iron. |
| Vitamin B6 deficiency | Vitamin B6 (pyridoxal phosphate) is a cofactor of erythroid 5-aminolevulinate synthase (ALAS2), the first enzyme of porphyrin synthesis. |
| Lead poisoning | Lead inhibits ferrochelatase and most of the other enzymes in the heme biosynthetic pathway to varying degrees. |
| Arsenic poisoning | Arsenic causes mitochondrial dysfunction, increased intracellular ROS, mitochondrial DNA (mtDNA) damage, and decreased activity of cytochrome c oxidase (COX). |
| Copper deficiency | Copper is an essential component of COX, ie, complex IV of the mitochondrial respiratory chain. Copper deficiency can thus impair mitochondrial O2 consumption and may lead to oxidation of Fe2+ to Fe3+, which cannot be used for heme synthesis. |
| Zinc overdose | Copper deficiency can be induced by excessive zinc ingestion because large quantities of ingested zinc interfere with intestinal copper absorption. |
| Isoniazid | Isoniazid deprives ALAS2 of pyridoxal phosphate and therefore inhibits porphyrin synthesis. |
| Chloramphenicol | This antibiotic not only inhibits bacterial but also mitochondrial protein synthesis via its action on the large ribosomal subunit of the organelle, thereby impairing the synthesis of respiratory chain subunits encoded by the mitochondrial genome. |
| Linezolid | Linezolid also inhibits mitochondrial protein synthesis by binding to human mitochondrial 16S ribosomal RNA. Certain mitochondrial haplogroups are more susceptible to this effect than others. |
| Alcohol abuse | Alcohol and its metabolite, acetaldehyde, can inhibit several steps of the heme synthetic pathway. Mitochondrial iron accumulation seems to reflect an imbalance between the large amounts of iron imported into mitochondria for heme synthesis, and insufficient production of protoporphyrin IX to incorporate the iron. |
| Vitamin B6 deficiency | Vitamin B6 (pyridoxal phosphate) is a cofactor of erythroid 5-aminolevulinate synthase (ALAS2), the first enzyme of porphyrin synthesis. |
| Lead poisoning | Lead inhibits ferrochelatase and most of the other enzymes in the heme biosynthetic pathway to varying degrees. |
| Arsenic poisoning | Arsenic causes mitochondrial dysfunction, increased intracellular ROS, mitochondrial DNA (mtDNA) damage, and decreased activity of cytochrome c oxidase (COX). |
| Copper deficiency | Copper is an essential component of COX, ie, complex IV of the mitochondrial respiratory chain. Copper deficiency can thus impair mitochondrial O2 consumption and may lead to oxidation of Fe2+ to Fe3+, which cannot be used for heme synthesis. |
| Zinc overdose | Copper deficiency can be induced by excessive zinc ingestion because large quantities of ingested zinc interfere with intestinal copper absorption. |
| Isoniazid | Isoniazid deprives ALAS2 of pyridoxal phosphate and therefore inhibits porphyrin synthesis. |
| Chloramphenicol | This antibiotic not only inhibits bacterial but also mitochondrial protein synthesis via its action on the large ribosomal subunit of the organelle, thereby impairing the synthesis of respiratory chain subunits encoded by the mitochondrial genome. |
| Linezolid | Linezolid also inhibits mitochondrial protein synthesis by binding to human mitochondrial 16S ribosomal RNA. Certain mitochondrial haplogroups are more susceptible to this effect than others. |