Pyridoxine dependent epilepsy (PDE) is caused by mutations in the ALDH7A1 gene (PDE-ALDH7A1) encoding α-aminoadipic-semialdehyde-dehydrogenase enzyme in the lysine catabolic pathway resulting in an accumulation of α-aminoadipic-acid-semialdehyde (α-AASA). We present the one-year treatment outcome of a patient on a lysine-restricted diet. Serial cerebral-spinal-fluid (CSF) α-AASA and CSF pipecolic-acid levels showed decreased levels but did not normalize. He had a normal neurodevelopmental outcome on a lysine-restricted diet. Despite normal CSF and plasma tryptophan levels and normal tryptophan intake, he developed mild CSF serotonin deficiency at one year of therapy. Stricter lysine restriction would be necessary to normalize CSF α-AASA levels, but might increase the risks associated with the diet. Patients are at risk of cerebral serotonin deficiency and should be monitored by CSF neurotransmitter measurements.
Keywords: 5-HIAA, 5-hydroxyindolacetic acid; Alpha-amino adipic acid semialdehyde dehydrogenase deficiency; CNS, central nervous system; CSF, cerebral spinal fluid; CSF-PA, CSF PA; CSF-α-AASA, CSF α-AASA; GA-I, glutaric aciduria type I; HVA, homovanillic acid levels; Lysine restricted diet; MSEL, Mullen Scales of Early Learning; P5CR, pyrroline-5-carboxylate reductase; P6C, piperidine 6-carboxylic acid; PA, pipecolic acid; PDE, pyridoxine dependent epilepsy; PDE-ALDH7A1, PDE caused by ALDH7A1 genetic defect; PDMS-2, Peabody Developmental Motor Scales — 2nd Edition; Pyridoxine dependent epilepsy; α AASAS, α-AASA synthase; α-AASA, alpha-aminoadipic acid semialdehyde; α-AASAD, alpha-aminoadipic acid semialdehyde dehydrogenase.