Mol Genet Metab. 2025 Jun 9;145(4):109170. doi: 10.1016/j.ymgme.2025.109170. Online ahead of print.
ABSTRACT
Pyridoxine dependent epilepsy due to Antiquitin deficiency (PDE-ALDH7A1) is a disorder of lysine catabolism that results in accumulation of α- aminoadipic semialdehyde (α-AASA) and Δ1-piperideine 6-carboxylic acid (P6C). It is hypothesised that these metabolites are neurotoxic and that chronic exposure may have detrimental long-term effects, particularly on the young developing brain. Lysine reduction therapies in the form of lysine restricted diet (LRD) and arginine, have been used as an adjunct to pyridoxine for the treatment of PDE-ALDH7A1 for the last 15 years with an aim to improve long-term developmental outcomes by reducing α-AASA and P6C. We present the management and outcomes for a cohort of 17 PDE-ALDH7A1 patients from our centre. In this study we show that LRD leads to a reduction in plasma lysine levels and urine α-AASA concentrations and a correlation between these is seen in individual patients, supporting the treatment hypothesis. LRD alone was shown to be sufficient to reduce plasma lysine into the target treatment range and addition of arginine was not required. Transition to LRD and long-term adherence is easier to achieve in patients under 6 months of age, compared to older patients. Lysine reduction therapies did not offer any additional benefit on seizure control over pyridoxine monotherapy but in keeping with previous studies, this study supports early initiation of LRD in patients under 6 months with cognitive function scores maintained in some, although longer term follow up is required and ongoing.
PMID:40680317 | DOI:10.1016/j.ymgme.2025.109170
