Two novel ALDH7A1 (antiquitin) splicing mutations associated with pyridoxine‐dependent seizures

Pyridoxine-dependent seizures (PDS) is a rare autosomal recessive disorder causing intractable seizures in neonates and infants. Patients are typically resistant to conventional anticonvulsants but respond well to the administration of pyridoxine. We report two unrelated patients affected with PDS as a result of alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency caused by pathogenic ALDH7A1/antiquitin mutations. Two of the three reported mutations are novel and result in erroneous splicing, as showed by messenger RNA (mRNA) studies. So far, the vast majority of the patients clinically diagnosed as PDS show alpha-AASA dehydrogenase deficiency, caused by mutations in the ALDH7A1 gene. However, despite the availability of reliable biomarkers, early consideration of a pyridoxine trial is still the most important issue in a child with therapy-resistant seizures.