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

Pasquale Striano1, Silvia Battaglia, Lucio Giordano

  • 1Department of Neurological Sciences, Epilepsy Center, Federico II University, Napoli, Italy. pstriano@email.it

Epilepsia
|August 23, 2008
PubMed

Insights

Pyridoxine-dependent seizures (PDS) are caused by ALDH7A1 gene mutations leading to alpha-aminoadipic semialdehyde dehydrogenase deficiency. Early pyridoxine treatment is crucial for infants with therapy-resistant seizures.

Area of Science:

  • Biochemistry
  • Genetics
  • Neurology

Background:

  • Pyridoxine-dependent seizures (PDS) is a rare genetic disorder characterized by intractable seizures in neonates and infants.
  • Patients often exhibit resistance to conventional anticonvulsant therapies.
  • PDS is typically responsive to pyridoxine administration.

Observation:

  • This report details two unrelated patients diagnosed with PDS.
  • The patients' condition resulted from alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency.
  • This deficiency was linked to pathogenic mutations in the ALDH7A1/antiquitin gene.

Findings:

  • Two novel mutations within the ALDH7A1 gene were identified in the patients.
  • Messenger RNA (mRNA) studies confirmed that these mutations lead to erroneous splicing.
  • The majority of clinically diagnosed PDS cases are associated with alpha-AASA dehydrogenase deficiency due to ALDH7A1 mutations.

Implications:

  • Despite reliable biomarkers, prompt consideration of a pyridoxine trial remains paramount for infants presenting with therapy-resistant seizures.
  • Understanding the genetic basis of PDS aids in diagnosis and management.
  • Identification of novel mutations expands the known mutational spectrum for ALDH7A1.

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