Background: Aminoacyl-tRNA synthetases (ARSs) are a group of enzymes responsible for the first step of protein translation. Among them, the KARS1 gene encodes lysyl-tRNA synthetase 1, an enzyme essential for charging tRNA-Lys with lysine in both the cytoplasm and mitochondria. Mutations in KARS1 are associated with a wide range of clinical phenotypes, including leukoencephalopathy, hereditary deafness, peripheral neuropathies, and multisystemic involvement. Methods: We hereby report a detailed case study of a 15-month-old boy presenting at age 5 months with developmental delay, microcephaly, hypotonia, sensorineural deafness, retinopathy, visual impairment, nystagmoid eye movements, and hepatic and immuno-hematological abnormalities. In addition, he exhibited a severe hyperkinetic movement disorder, not previously reported in the literature, and developed epilepsy at 13 months. Genetic testing identified two rare compound heterozygous variants in the KARS1 gene. Results: With this report, we aim to contribute to the expanding of both the clinical phenotype and the allelic spectrum of lysyl-tRNA synthetase-related disorders. Our study also includes a review of previously described KARS1 cases presenting with movement disorders. Conclusions: Our findings further highlight the importance of assessing systemic involvement and performing brain and spinal neuroimaging, as well as implementing genetic screening, in infants presenting with global developmental delay, sensory deficits, and movement disorders—features that may suggest a mitochondrial disorder such as those involving ARS mutations.

Background/Objectives: Biologic therapies are the cornerstone of severe asthma management. However, evidence regarding switching between biologics in children with severe asthma remains limited. Methods: Retrospective observational study including patients aged 6–17 years with severe asthma, followed at our tertiary referral center, who switched biologic therapy. Clinical, laboratory, and lung function data were collected at the initiation of the second biologic (T0) and after 4 (T1) and 12 months (T2). Changes in asthma control, exacerbation rate, inhaled corticosteroid dose, FeNO and lung function were evaluated. Results: Eight patients who switched and had been treated with a second biologic for at least 12 months were included. Switching occurred from omalizumab to dupilumab (n = 1), mepolizumab to dupilumab (n = 5), and mepolizumab to omalizumab (n = 2). The main reason for switching was inadequate asthma control, while one patient switched because of poorly controlled comorbidity. At T2, exacerbations significantly decreased (p = 0.03), with significant improvements in FEV₁ (p = 0.002) and FEV₁/FVC (p = 0.015). The daily fluticasone-equivalent dose decreased from a median of 500 μg to 425 μg. Conclusions: In this cohort, switching biologic therapy was associated with improved clinical and functional outcomes, with a significant response already detectable after 4 months. These findings highlight the importance of close clinical and functional monitoring to identify children who may benefit from a change in biologic therapy. Larger prospective studies are needed to define standardized criteria and optimal timing for biologic switching in pediatric severe asthma.