Monthly Archives: July 2017
Sarah Weatherspoon, William A. Langley, Kelly Ward, Kristie Patterson, Peter L. Nagy, Keith HylandPNPO deficiency is an autosomal recessive disorder that leads to pyridoxal 5’-phosphate deficiency and typically results in neonatal or early onset seizures. The latest age reported for presentation is 5 months in an infant with infantile spasms (Mills et al 2014). Here we reemphasize that PNPO deficiency can respond to pyridoxine and demonstrate that the disorder can present with seizures that first occur after nine months of life. Methods: CSF pyridoxal 5’-phosphate measurement and NGS analysis of the PNPO gene were performed using standard methodologies (Medical Neurogenetics Laboratories) Results: A male child with mild speech delay initially presented with febrile seizures at 10 months of age, followed by nonfebrile convulsive seizures and myoclonic atonic seizures. The patient was admitted for EEG monitoring at 15 months, during which time he developed non convulsive status epilepticus that resolved with phenobarbital. However, he remained severely encephalopathic. Pyridoxine and folinic acid were started empirically while awaiting test results. The encephalopathy resolved after 4 days. Analysis of CSF showed slightly decreased pyridoxal 5’-phosphate (14 nmol/l: ref. range 15-51); neurotransmitter metabolites, alpha aminoadipic semialdehyde and amino acids were unremarkable. NGS analysis revealed two heterozygous pathogenic variants in the PNPO gene (Asp33Val and Arg141Cys). Both variants have been previously associated with pyridoxine responsive PNPO deficiency and in vitro expression studies have demonstrated the activity of each to be approximately 50% of the wild type PNPO activity.
Ymkje Cuperus, MS Senior Genetic Counselor We are excited to announce that Ymkje Cuperus, MS has joined MNG Laboratories as our Senior Genetic Counselor! Ymkje hails from the Netherlands and obtained her RN at UMC Sint Radboud Nijmegen, her BHA in Health Management at Hogeschool Arnhem/Nijmegen, and her MS in Health Science at Utrecht University. She obtained her genetic counseling training at UMC Utrecht and is a founding member of the Dutch Genetic Counselor’s Society. Ymkje was most recently with EGL Genetics where she spent the past 8 years in various genetic counseling roles and served departments such as the biochemical, molecular and cytogenetic divisions. Before coming to the US in 2009, Ymkje was a clinical genetic counselor at the University Medical Center at Utrecht and prior to entering the genetic counselor field, she worked as a Sr. Nurse Manager at Groot Klimmendaal, Children Rehabilitation Center, where she supervised nursing care and rehabilitation for children and their families. Ymkje has developed a strong reputation and interest in the fields of molecular testing that are an excellent fit for MNG. With over 20 years’ experience in the field of genetic counseling, we warmly welcome Ymkje to our team and look forward to her helping us make a difference for the patients we all serve in neurogenetics.