**3.4 Defects in PLP-dependent enzymes**

In addition to its coenzymatic role, binding of PLP to its apo-enzymes may also be required for proper folding and correct subcellular targeting of these enzymes [6, 150]. Several inborn errors affecting PLP-dependent enzymes have been described to benefit from PN therapy. Examples are homocystinuria (cystathionine β-synthase deficiency), X-linked sideroblastic anemia (δ-aminolevulinate synthase deficiency), primary hyperoxaluria type I (alanine: glyoxylate aminotransferase (AGT) deficiency), ornithine aminotransferase deficiency and AADC deficiency [6, 9, 150]. The therapeutic effect of PN supplementation could to be attributed to the chaperone-like, stabilizing action of PLP on these mutated proteins [150]. In primary hyperoxaluria type I, it has been hypothesized that at high concentration, PLP promotes AGT dimerization and inhibit the accumulation of monomeric protein species which are mistargeted to the mitochondria [6, 150]. A recent addition to this category of PN-responsive disorders came from the discovery of *GOT2* mutations in patients who presented with a novel form of epileptic encephalopathy and serine deficiency [151]. *GOT2* encodes the PLP-dependent enzyme glutamate oxaloacetate transaminase (mitochondrial isoform). PN supplementation, either alone or in combination with serine, led to seizure control in these patients [151].
