Objective: To describe a new phenotype and the diagnostic workup of a vitamin-B6-dependent epilepsy due to PLPBP deficiency in an infant with early-onset epilepsy at age 5 ½ months.
Methods: 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 bi-allelic inheritance. The clinical phenotype and course of disease were compared to the 44 cases reported in the literature, harboring variants in PLPHP and with cases of vitamin-B6-dependent epilepsy due to other known causative genes.
Results: 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.
Conclusions: We here describe a previously unreported individual harboring bi-allelic pathogenic PLPHP variants presenting with paroxysmal eye-head-movements followed by epileptic spasms and an almost normal interictal electroencephalogram (EEG), 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.
A plan of action was established following certain given guidelines:-The replica should have the same geometrical dimensions as the original rock. -It should be fi xed in the same position as the original rock. -It should be situated at the same place on Cerro La Movediza. -It should consist of a steel structure and it should be coated with a composite material capable of reproducing the colour and texture of the original rock.
Activities
Topographic StudiesThe planialtimetric topographic surveys determined the position and location of the replica. The geometry of the replica was determined from an analysis of the available information and from the survey of the geometry of the fallen rock that lies at the foot of the Cerro La Movediza. Infrared rays, laser electronic tachometres and GPS receiver systems were used to this end. 1523 points among the three exist-ing pieces of rock were surveyed in a planialtimetric way. The study showed that the rock had an approximate volume of 91 m 3 , an approximate weight of 248 tons and an external surface of approximately 133 m 2 .
Geological and Geotechnical SurveysThese studies included, on one hand, the evaluation of the hill discontinuities existing in the location. It was observed that the hill had a fissure, the geological and geotechnical characteristics of which were studied, leading to the conclusion that this did not, in any way, render the task of anchoring the replica to the hill impossible.On the other hand, the characteristics of the rock base, which determined the depth of anchors and their size, were studied. It was reported that the solid rock on the hill had a granite structure and that it presented very good geological characteristics 2 ideal for anchoring the replica.
Wind Tunnel StudyThis study allowed the assessment of the impact of the topography on the location and the geometry of the structure in the distribution of the wind pressure. The static and dynamic forces at the anchoring for each direction of the wind were also measured. The range of standard frequencies where higher levels of non-stationary aerodynamic load can be found was also determined.
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