title: Two novel ALDH7A1 (antiquitin) splicing mutations associated with pyridoxine-dependent seizures.
abstract: 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.
authors: Department of Neurological Sciences, Epilepsy Center, Federico II University, Napoli, Italy. pstriano@email.it
authors: Pasquale
authors: P
authors: Striano
authors: Silvia
authors: S
authors: Battaglia
authors: Lucio
authors: L
authors: Giordano
authors: Giuseppe
authors: G
authors: Capovilla
authors: Francesca
authors: F
authors: Beccaria
authors: Eduard A
authors: EA
authors: Struys
authors: Gajja S
authors: GS
authors: Salomons
authors: Cornelis
authors: C
authors: Jakobs
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010597:Pharmacogenetics; D011736:Pyridoxine / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy / Q000235:genetics*; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D014803:Vitamin B Complex; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; D011736:Pyridoxine