Figure 2.

Pathways and genes implicated in CSA. Mitochondrial pathways relevant to the pathogenesis of CSA are diagrammed. Synthetic pathways are indicated by black dashed lines, whereas pathways whose products are required for other pathways implicated in CSA are shown in gray lines. Heme biosynthetic, iron-sulfur cluster biogenesis, mitochondrial (MT) translation, and oxidative phosphorylation/mitochondrial respiration pathways and the genes mutated in CSA in those pathways are highlighted in distinct colors. Thiamine-responsive megaloblastic anemia (TRMA) affects multiple pathways dependent upon thiamine. CP, coproporphyrin; Gly, glycine; MLASA, mitochondrial myopathy with lactic acidosis and SA; mtDNA, mitocondrial DNA; PMPS, Pearson marrow-pancreas syndrome; PPIX, protoporphyrin IX; TCA, tricarboxylic acid. Modified from Fleming⁷ with permission.