Journal article
Confirmation of mutations in PROSC as a novel cause of vitamin B 6 -dependent epilepsy.
- Plecko B Division of Child Neurology, University Children's Hospital Zurich, Zurich, Switzerland.
- Zweier M Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.
- Begemann A radiz - "Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases University of Zurich", University of Zurich, Zurich, Switzerland.
- Mathis D Clinical Chemistry, University Children's Hospital Zurich, Zurich, Switzerland.
- Schmitt B Division of Child Neurology, University Children's Hospital Zurich, Zurich, Switzerland.
- Striano P Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, G. Gaslini Institute, Genova, Italy.
- Baethmann M Sozialpädiatrisches Zentrum, Dritter Orden, München-Nymphenburg, Munich, Germany.
- Vari MS Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, G. Gaslini Institute, Genova, Italy.
- Beccaria F Child Neuropsychiatry, C. Poma Hospital, Mantova, Italy.
- Zara F IRCCS, University of Genova, G. Gaslini Institute, Genova, Italy.
- Crowther LM Division of Child Neurology, University Children's Hospital Zurich, Zurich, Switzerland.
- Joset P Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.
- Sticht H Institute of Biochemistry, University of Erlangen-Nuernberg, Erlangen, Germany.
- Papuc SM radiz - "Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases University of Zurich", University of Zurich, Zurich, Switzerland.
- Rauch A radiz - "Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases University of Zurich", University of Zurich, Zurich, Switzerland.
- 2017-04-10
Published in:
- Journal of medical genetics. - 2017
PROSCexome sequencing.
inborn errors of metabolism
neonatal seizures
pyridoxine
vitamin B6
Adolescent
Adult
Alleles
Child
Child, Preschool
Consanguinity
DNA Mutational Analysis
Electroencephalography
Epilepsy
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Humans
Male
Mutation
Phenotype
Proteins
Pyridoxine
Vitamin B 6
English
Vitamin-B6-dependent epilepsies are a heterogenous group of treatable disorders due to mutations in several genes (ALDH7A1, PNPO, ALPL or ALDH4A1). In neonatal seizures, defects in ALDH7A1 and PNPO explain a major fraction of cases. Very recently biallelic mutations in PROSC were shown to be a novel cause in five families. We identified four further unrelated patients harbouring a total of six different mutations, including four novel disease mutations. Vitamin B6 plasma profiles on pyridoxine did not enable the differentiation of patients with PROSC mutations. All four patients were normocephalic and had normal cranial imaging. Pyridoxine monotherapy allowed complete seizure control in one, while two patients had occasional febrile or afebrile seizures and one needed additional valproate therapy for photosensitive seizures. Two patients underwent a controlled pyridoxine withdrawal with signs of encephalopathy within a couple of days. Three had favourable outcome with normal intellectual properties at age 12.5, 15.5 and 30 years, respectively, while one child had marked developmental delay at age 27 months. The clinical and electroencephalographic phenotype in patients with PROSC mutations was indistinguishable from ALDH7A1 and PNPO deficiency. We therefore confirm PROSC as a novel gene for vitamin-B6-dependent epilepsy and delineate a non-specific plasma vitamin B6 profile under pyridoxine treatment.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1136/jmedgenet-2017-104521
- PMID 28391250
- Persistent URL
- https://sonar.ch/global/documents/88602
Export to…
Statistics
Document views: 71
File downloads: