[NEXT-GENERATION SEQUENCING PERFORMED IN PATIENTS RAISING THE SUSPICION OF AN INBORN ERROR OF METABOLISM UNCOVERED A HOMOZYGOUS VARIANT IN YARS1 ALLOWING A NOVEL THERAPEUTIC TRIAL].

INTRODUCTION: Inborn-Errors of Metabolism (IEM) are genetic disorders resulting from mutations in genes encoding proteins involved in biochemical-metabolic pathways. However, some IEMs lack specific biochemical markers. Early incorporation of next-generation-sequencing (NGS) including whole exome sequencing (WES) into the diagnostic algorithm of IEMs herein provided, increases diagnostic accuracy, permits genetic counseling and improves therapeutic options. This is exemplified by diseases affecting aminoacyl-tRNA synthetases (ARSs), enzymes involved in protein translation. Recent studies showed that supplementing amino-acids to cell-culture and patients with ARSs deficiencies resulted in improvement of biochemical and clinical parameters, respectively.

Spontaneous movements, motor milestones, and temperament of preterm-born infants: Associations with mother-infant attunement.

Preterm-born infants and their mothers are at higher risk of showing less attuned interactions. We sought to identify characteristics of preterm-born infants associated with the attunement of mother-infant interactions at the corrected ages of 3-4 months, looking specifically at motor behaviors. We focused on infants' spontaneous movements, achievement of motor milestones, and temperament, which at this young age is often manifested via movement. Sixty preterm-born infants (Mdngestation age in weeks  = 33, 57.38% male, corrected age Mdn = 14 weeks, interquartile range = 13-16) and their mothers participated. Independent observers rated mother-infant attunement, infants' spontaneous movements, and infants' achievement of motor milestones. Mothers reported infant temperament. We found infants' smooth and fluent movement character and continual fidgety movements were associated with better attunement in terms of higher maternal sensitivity and non-intrusiveness and higher infant responsiveness and involvement. Unexpectedly, infants' achievement of motor milestones was not significantly associated with mother-infant attunement, and maternal reports of infants' higher soothability were associated with lower maternal sensitivity. The study illustrates the value of including the assessment of infants' spontaneous movements, designed for early detection of neurological deficiencies, in research and in clinical practice with parents and preterm-born infants.