Case report: PLPHP deficiency, a rare but important cause of B6-responsive disorders: A report of three novel individuals and review of 51 cases

Sarah Alsubhi; Bradley Osterman; Nicolas Chrestian; François Dubeau; Daniela Buhas; Myriam Srour

doi:10.3389/fneur.2022.913652

Case report: PLPHP deficiency, a rare but important cause of B6-responsive disorders: A report of three novel individuals and review of 51 cases

Front Neurol. 2022 Oct 17:13:913652. doi: 10.3389/fneur.2022.913652. eCollection 2022.

Authors

Sarah Alsubhi¹, Bradley Osterman¹, Nicolas Chrestian², François Dubeau³, Daniela Buhas^{4

5}, Myriam Srour^{1

3

6}

Affiliations

¹ Division of Pediatric Neurology, Department of Pediatrics, McGill University, Montreal, QC, Canada.
² Department of Pediatric Neurology, Pediatric Neuromuscular Disorder, Centre Mère Enfant Soleil, Laval University, Quebec City, QC, Canada.
³ Department of Neurology and Neurosurgery McGill University, Montreal, QC, Canada.
⁴ Division of Medical Genetics, Department of Specialized Medicine, McGill University Health Center, Montreal, QC, Canada.
⁵ Department of Human Genetics, McGill University, Montreal, QC, Canada.
⁶ Child Health and Human Development Program (CHHD), McGill University Health Center Research Institute, Montreal, QC, Canada.

Abstract

PLPHP (pyridoxal-phosphate homeostasis protein) deficiency is caused by biallelic pathogenic variants in PLPBP and is a rare cause of pyridoxine-responsive disorders. We describe three French-Canadian individuals with PLPHP deficiency, including one with unusual paroxysmal episodes lacking EEG correlation with a suspicious movement disorder, rarely reported in B6RDs. In addition, we review the clinical features and treatment responses of all 51 previously published individuals with PLPHP deficiency. Our case series underlines the importance of considering PLPBP mutations in individuals with partially B6-responsive seizures and highlights the presence of a founder effect in the French-Canadian population.

Keywords: B6; B6RDs; PLPBP; PLPHP; PROSC; pyridoxine; seizures; status epilepticus.

Publication types

Case Reports