Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Gallagher, RC; Van Hove, JL; Scharer, G; Hyland, K; Plecko, B; Waters, PJ; Mercimek-Mahmutoglu, S; Stockler-Ipsiroglu, S; Salomons, GS; Rosenberg, EH; Struys, EA; Jakobs, C.
Folinic acid-responsive seizures are identical to pyridoxine-dependent epilepsy.
Ann Neurol. 2009; 65(5):550-556
Doi: 10.1002/ana.21568
(- Case Report)
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Plecko Barbara
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- Abstract:
- Folinic acid-responsive seizures and pyridoxine-dependent epilepsy are two treatable causes of neonatal epileptic encephalopathy. The former is diagnosed by characteristic peaks on cerebrospinal fluid (CSF) monoamine metabolite analysis; its genetic basis has remained elusive. The latter is due to alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency, associated with pathogenic mutations in the ALDH7A1 (antiquitin) gene. We report two patients whose CSF showed the marker of folinic acid-responsive seizures, but who responded clinically to pyridoxine. We performed genetic and biochemical testing of samples from these patients, and seven others, to determine the relation between these two disorders. CSF samples were analyzed for the presence of alpha-AASA and pipecolic acid. DNA sequencing of the ALDH7A1 gene was performed. Both patients reported here had increased CSF alpha-AASA, CSF pipecolic acid, and known or likely pathogenic mutations in the ALDH7A1 gene, consistent with alpha-AASA dehydrogenase deficiency. Analysis of CSF samples from seven other anonymous individuals diagnosed with folinic acid-responsive seizures showed similar results. These results demonstrate that folinic acid-responsive seizures are due to alpha-AASA dehydrogenase deficiency and mutations in the ALDH7A1 gene. Thus, folinic acid-responsive seizures are identical to the major form of pyridoxine-dependent epilepsy. We recommend consideration of treatment with both pyridoxine and folinic acid for patients with alpha-AASA dehydrogenase deficiency, and consideration of a lysine restricted diet. The evaluation of patients with neonatal epileptic encephalopathy, as well as those with later-onset seizures, should include a measurement of alpha-AASA in urine to identify this likely underdiagnosed and treatable disorder.
- Find related publications in this database (using NLM MeSH Indexing)
- Aldehyde Dehydrogenase - genetics
- Biogenic Monoamines - cerebrospinal fluid
- DNA Mutational Analysis -
- Humans -
- Infant -
- Leucovorin - therapeutic use
- Linear Models -
- Lysine - genetics
- Male -
- Mutation - genetics
- Pipecolic Acids - cerebrospinal fluid
- Pyridoxine - therapeutic use
- Seizures - cerebrospinal fluid
- Seizures - drug therapy
- Seizures - genetics
- Tandem Mass Spectrometry - methods
- Vitamin B Complex - therapeutic use