Clinical Spectrum in Children With Pyridoxine-Dependent Epilepsy

Abstract

Research Article| May 01 2013 Clinical Spectrum in Children With Pyridoxine-Dependent Epilepsy AAP Grand Rounds (2013) 29 (5): 55. https://doi.org/10.1542/gr.29-5-55 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Clinical Spectrum in Children With Pyridoxine-Dependent Epilepsy. AAP Grand Rounds May 2013; 29 (5): 55. https://doi.org/10.1542/gr.29-5-55 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: epilepsy, pyridoxine dependency syndrome, seizures, pyridoxine Source: Perez B, Gutierrez-Solana LG, Verdu A, et al. Clinical, biochemical, and molecular studies in pyridoxine-dependent epilepsy: antisense therapy as possible new therapeutic option. Epilepsia. 2013; 54(2): 239– 248; doi: https://doi.org/10.1111/epi.12083Google Scholar Researchers in Spain and India studied the clinical, biochemical, and genetic spectrum in children with pyridoxine-dependent epilepsy (PDE). The disease was confirmed based on the presence of α-aminoadipic semialdehyde (α-AASA) in urine and pipecolic acid (PA) in plasma and/or cerebrospinal fluid, and by DNA analysis. A total of 12 children were included in the case series. Onset of seizures varied from the neonatal period to the first months of life. Seizures were focal or multifocal, clonic or myoclonic, and generalized tonic; 50% of study patients had status epilepticus. Seizures were controlled transiently with conventional antiepileptic drugs (AED) for 15 or more days in 8 of 12 patients, leading to a delay in diagnosis. The effective dose of pyridoxine (vitamin B6) to suppress seizures ranged from 10 to 30 mg/kg per day. Refractory neonatal seizures were the main indications for suspecting and starting treatment for PDE. Neurologic symptoms in addition to seizures included hypotonia, irritability, and psychomotor retardation. EEG abnormalities were variable in the study children; the EEG was normal in 1 patient. All EEGs became normal after pyridoxine therapy. MRI abnormalities included mega cisterna magna, Dandy Walker syndrome, ventriculomegaly, and corpus callosum dysgenesis. Six study children, followed for more than 5 years, had evidence of cognitive dysfunction. Delay in treatment and dysgenesis of the corpus callosum were risk factors for neurodevelopmental delay. Treatment with pyridoxine failed to normalize IQ. The authors conclude that, despite pyridoxine therapy, there remains a need to reduce persistent neurologic damage in PDE, and that the diagnosis of PDE should be considered in infants with intractable or poorly controlled seizures. Dr Millichap has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. PDE is an autosomal recessive inherited disorder caused by mutations in the ALDH7A1 gene, which encodes antiquitin protein. The clinical spectrum of antiquitin deficiency extends from ventriculomegaly detected on fetal ultrasound, through abnormal fetal movements, to the onset of seizures after birth.1 Clinical diagnosis of PDE can be challenging, because (1) there may be some response to AEDs, (2) response to pyridoxine may not be instantaneous, and (3) structural brain abnormalities may coexist.1 PDE should be considered in the differential diagnosis of any infant with intractable seizures, including patients with MRI abnormalities such as corpus callosum dysgenesis or Dandy Walker syndrome. In suspected cases of PDE, the use of biochemical and DNA tests for antiquitin deficiency is recommended together with a clinical trial of pyridoxine.1 The long-term outcome of PDE is often poor. In a Dutch PDE cohort of 14 patients,2 mental development was delayed in the majority of children, with a median IQ of 72; only 5 walked at 2... You do not currently have access to this content.