Pyridoxine dependent epilepsy: Is late onset a predictor for favorable outcome?

de Rooy RLP; Halbertsma FJ; Struijs EA; van Spronsen FJ; Lunsing RJ; Schippers HM; van Hasselt PM; Plecko B; Wohlrab G; Whalen S; Benoist JF; Valence S; Mills PB; Bok LA

doi:10.1016/j.ejpn.2018.03.009

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Journal article

Pyridoxine dependent epilepsy: Is late onset a predictor for favorable outcome?

de Rooy RLP Department of Pediatrics, Zuyderland Hospital, Heerlen, The Netherlands.
Halbertsma FJ Department of Pediatrics, Màxima Medical Center, Veldhoven, The Netherlands.
Struijs EA Metabolic Unit, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
van Spronsen FJ Department of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Lunsing RJ Department of Child Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Schippers HM Department of Neurology, Sint Antonius Ziekenhuis, Nieuwegein, Utrecht, The Netherlands.
van Hasselt PM Department of Pediatric Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands.
Plecko B Division of Neurology, Children's Hospital, University of Zurich, Zurich, Switzerland.
Wohlrab G Division of Neurology, Children's Hospital, University of Zurich, Zurich, Switzerland.
Whalen S UF de génétique clinique, APHP, Hôpital Armand Trousseau, Paris, France.
Benoist JF Centre de Référence des Maladies Héréditaires du Métabolisme, Service de Biochimie-Hormonologie, Hôpital Robert Debré, Paris, France.
Valence S Department of Child Neurology, APHP, Armand Trousseau Hospital, Paris, France.
Mills PB Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, United Kingdom.
Bok LA Department of Pediatrics, Màxima Medical Center, Veldhoven, The Netherlands. Electronic address: l.bok@mmc.nl.

2018-04-18

Published in:

European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. - 2018

English AIM
In pyridoxine dependent epilepsy (PDE), patients usually present with neonatal seizures. A small subgroup is characterized by late-onset beyond 2 months of age. We aim to analyze the observation of relatively good cognitive outcome in this subgroup of late-onset PDE patients.

METHODS
We retrospectively analyzed data from four metabolically and genetically confirmed late-onset patients with PDE due to antiquitin (ALDH7A1) deficiency. Data were analyzed regarding ALDH7A1 mutations, alpha-Aminoadipic semialdehyde (α-AASA) and pipecolic acid (PA) levels, medication during pregnancy, delivery, treatment delay, amount of seizures, pyridoxine dose, adjuvant therapy and findings on brain MRI.

RESULTS
Results showed that three patients had relatively good outcome (IQ 80-97), while one patient did not undergo formal testing and was considered mildly delayed. We were unable to find a clear association between the above-mentioned variables and cognitive outcome, although a less severe genotype may be present in three patients, and maternal medication could be accountable for better outcome in two patients.

INTERPRETATION
We suggest that favorable outcome in late onset PDE might be explained by a combination of factors. A yet unknown protective factor, different genetic variations, functional variation and secondarily variation in treatment regimens and absence of neonatal seizure induced brain damage.

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