Affiliations 

  • 1 Department of Pediatrics JA Toride General Hospital Toride Japan
  • 2 Department of Human Genetics Yokohama City University Graduate School of Medicine Yokohama Japan
  • 3 Department of Pediatrics Yokohama City University Medical Center Yokohama Japan
  • 4 Department of Paediatrics Sarawak General Hospital Kuching Malaysia
  • 5 Department of Genetics Hospital Kuala Lumpur Kuala Lumpur Malaysia
  • 6 Department of Child Neurology Comprehensive Epilepsy Center Seirei-Hamamatsu General Hospital Shizuoka Japan
  • 7 Department of Neurosurgery Comprehensive Epilepsy Center Seirei-Hamamatsu General Hospital Hamamatsu Japan
  • 8 Department of Biochemistry Hamamatsu University School of Medicine Hamamatsu Japan
  • 9 Department of Pediatrics Showa University School of Medicine Shinagawa-ku, Tokyo Japan
Epilepsia Open, 2018 Dec;3(4):495-502.
PMID: 30525118 DOI: 10.1002/epi4.12272

Abstract

Objective: Vitamin B6-dependent epilepsies are treatable disorders caused by variants in several genes, such as ALDH7A1,PNPO, and others. Recently, biallelic variants in PLPBP, formerly known as PROSC, were identified as a novel cause of vitamin B6-dependent epilepsies. Our objective was to further delineate the phenotype of PLPBP mutation.

Methods: We identified 4 unrelated patients harboring a total of 4 variants in PLPBP, including 3 novel variants, in a cohort of 700 patients with developmental and epileptic encephalopathies. Clinical information in each case was collected.

Results: Each patient had a different clinical course of epilepsy, with seizure onset from the first day of life to 3 months of age. Generalized tonic-clonic seizures were commonly noted. Myoclonic seizures or focal seizures were also observed in 2 patients. Interictal electroencephalography showed variable findings, such as suppression burst, focal or multifocal discharges, and diffuse slow activity. Unlike previous reports, all the patients had some degree of intellectual disability, although some of them had received early treatment with vitamin B6, suggesting that different mutation types influence the severity and outcome of the seizures.

Significance: PLPBP variants should be regarded as among the causative genes of developmental and epileptic encephalopathy, even when it occurs after the neonatal period. Early diagnosis and proper treatment with pyridoxine or pyridoxal phosphate is essential to improve the neurologic prognosis in neonates or young children with poorly controlled seizures.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.