Figure 1: Summary of the glyoxylate metabolism in human hepatocytes. Simplified pathways involving glycine, glycolate, and hydroxyproline as the main sources of glyoxylate. Peroxisomal glyoxylate is detoxified by AGT, while mitochondrial and cytosolic glyoxylate is reduced to glycolate by GRHPR, preventing excessive oxidation to oxalate by LDH. Hydroxyproline metabolism results in the production of 4-hydroxy-2-oxoglutarate that is normally split into glyoxylate and pyruvate by HOGA1. PyrrOHcarbox=pyrroline-5-carboxylate; HGlu= 4-hydroxy-glutamate; HO-Glu=4-hydroxy-2-oxoglutarate. The three genetic defects currently known to cause PH are inherited with autosomal recessive pattern. The genes involved are alanine-glyoxylate aminotransferase (AGXT, at 2q37.3, MIM*604285), for PH type I (PH1, MIM#259900), glyoxylate reductase/hydroxypyruvate reductase (GRHPR, at 9q12, MIM*604296), for PH type II (PH2, MIM#260000), and 4-hydroxy-2-oxoglutarate aldolase (HOGA1 at 10q24.2, MIM*613597), for PH type III (PH3, MIM#613616).