(1) Department of Neurology, Hospital Sant Joan de Déu, Barcelona, Spain
(2) Neuropediatrics Department, Hospital de D. Estefânia, CHLC;
(3) Molecular Medicine Institute, University of Lisbon, Portugal
(4) Department of Genetics and Biochemistry, Hospital Sant Joan de Déu, Barcelona, Spain (5) CIBER-ER (Biomedical Network Research Centre on Rare Diseases), Instituto de Salud Carlos III, Madrid, Spain
International Congress of Inborn Errors of Metabolism 2013, Barcelona, September 2013
Background: PNPO gene mutations can produce neonatal refractoryseizuresthatrespondtopyridoxalphosphate (PLP). PLP isthe active form of vitamin B6 and a cofactor of more than 120 enzymereactionsincludingneurotransmittermetabolism.
Objectives: To describe themainclinical and etiologicalfeatures of a series of 14 patientswith CSF vitamin B6 deficiency and their response to PLP treatment.
Patients and Methods: Clinical and geneticstudies of X patients (aged 1 dayto 8 years), withepilepticencephalopathy (butalsootherclinicalsigns) and lowvitamin B6 in the CSF (4-31nmol/L; N:32-78) are reported. Etiologieswerediverse: hypoxic-ischemicencephalopathy, chromosomalabnormalities, INAD and KCNQ2 mutations. 4 patientswith no etiological diagnosis hadnegative PNPO geneticstudy. Onepatienthadburstsuppressionpattern. Plasma PLP wasdecreased in 3 patients, plasma and CSF aminoacidswere normal. 3-orthometyldopa waselevated in 1 case. 5-HIIA, HVA, and GABA weredecreased in 8, 3 and 1 patientsrespectively. Nonehad anemia orevidence of malabsortionsyndrome. Anextensivemetabolicwork-up wasnegative. 12 weretreatedwithantiepilepticdrugsbeingvalproatethemostfrequentlyused. Response totreatmentResponse to treatment was positive for seizure control and cognitive performance in 5 of them, while the others showed no positive response or adverse efects (in 2 of them).
Conclusion/Discussion: Otherthan PNPO mutations, PLP depletion in the CSF could be duerelatedtodifferentclinicalsituationssuch as refractoryepilepsy and theprolonged use of some particular antiepilepticdrugs. PLP treatmentmayhavevery positive effectsregardlesstheetiology.