Schematic representation of mitochondrial pathways affected by genetic defects in congenital SAs. Genes mutated in congenital SAs (in red) are involved in several pathways: heme synthesis, mitochondrial iron homeostasis, tRNA biosynthesis. Nonsyndromic congenital SAs: 1, XLSA; 2, SLC25A38 deficiency; 5, glutaredoxin 5 deficiency; 6, erythropoietic protoporphyria. Syndromic congenital SAs: 3, thiamine-responsive megaloblastic anemia; 4, X-linked congenital SA with ataxia; 7, Pearson marrow-pancreas syndrome; 8, myopathy, lactic acidosis, and SA; 9. SA, SIFD. ABCB7, mitochondrial transporter for cytosolic Fe-S cluster; ALA, 5-aminlevulinic acid; ALAS2, d-aminolevulinate synthase 2; Co-A, coenzyme A; CP gen III, coproporphyrinogen III; FECH, ferrochelatase; GLRX5, glutaredoxin 5; PPIX, protoporphyrin IX; PUS1, pseudouridylate synthase 1; SLC19A2, transporter of TPP; SLC25A38, transporter of glycine; TPP, thiamine pyrophosphate; TRNT1, tRNA-nucleotidyltransferase 1.