Infantile Spasms without Hypsarrhythmia and Paroxysmal Eye–Head Movements in an Infant with a Pyridoxine-Dependent Epilepsy due to PLPBP/PLPHP Deficiency

Judith Kalser; Fabienne Giuliano; Maria Peralta; Barbara Plecko; Bigna K. Bölsterli

doi:10.1055/a-2003-9886

Neuropediatrics, Table of Contents

Neuropediatrics 2023; 54(06): 422-425
DOI: 10.1055/a-2003-9886

Short Communication

Infantile Spasms without Hypsarrhythmia and Paroxysmal Eye–Head Movements in an Infant with a Pyridoxine-Dependent Epilepsy due to PLPBP/PLPHP Deficiency

Judith Kalser

¹Pediatric Neurology and Neurorehabilitation Unit, Department of Woman-Mother-Child, Lausanne University Hospital, Lausanne, Switzerland

,

Fabienne Giuliano

²Division of Genetic Medicine, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland

,

Maria Peralta

³Pediatric Unit for Metabolic Diseases, Department of Woman-Mother-Child, Lausanne University Hospital, Lausanne, Switzerland

,

Barbara Plecko

⁴Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria

,

Bigna K. Bölsterli

⁵Child Development Center, University Children's Hospital Zurich, Zurich, Switzerland

⁶Department of Pediatric Neurology, University Children's Hospital Zurich, Zurich, Switzerland

⁷Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland

⁸Department of Pediatric Neurology, Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland

› Author Affiliations

Abstract

To describe a new phenotype and the diagnostic workup of a vitamin-B₆-dependent epilepsy due to pyridoxal 5′-phosphate-binding protein (PLPBP) deficiency in an infant with early-onset epilepsy at the age of 5 years 6 months. Following immediate and impressive clinical response to treatment with pyridoxine, metabolic screening for vitamin-B₆-dependent epilepsies and targeted next-generation sequencing (NGS)-based gene panel analysis were performed. Potentially pathogenic variants were confirmed by Sanger sequencing in the patient, and variants were analyzed in both parents to confirm biallelic inheritance. The clinical phenotype and course of disease were compared to the 44 cases reported in the literature, harboring variants in pyridoxal phosphate homeostasis protein (PLPHP) and with cases of vitamin-B₆-dependent epilepsy due to other known causative genes. Levels of alpha-aminoadipic semialdehyde in urine and amino acids were normal. Two inherited pathogenic variations in PLPHP were found in compound heterozygosity, including one novel deletion. We here describe a previously unreported individual harboring biallelic pathogenic PLPHP variants presenting with paroxysmal eye–head movements followed by epileptic spasms and an almost normal interictal electroencephalogram, thus expanding the clinical spectrum of PLPBP deficiency. This warrants consideration of vitamin-B₆-dependent epilepsies in patients with early-onset epilepsy, including epileptic spasms, and eye movement disorders also beyond the neonatal period even when metabolic screening for vitamin-B₆-dependent epilepsies is negative. PLPHP should be included systematically in NGS epilepsy gene panels.

Keywords

pyridoxine - vitamin B₆ - paroxysmal movement disorder - epilepsy - West's syndrome - PROSC

Full Text

References

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