Undiscovered Phenotype of KARS1 Related Mitochondrial Leukoencephalopathy

Abstract

Background: Infantile onset progressive leukoencephalopathy with or without deafness is an autosomal recessive neurodegenerative disorder with variable clinical presentation, manifesting in infancy or early childhood. This disorders is one of KARS1 gene mutation spectrum that results mostly from compound heterozygous mutations rather than homozygous mutations, resulting in a dysfunctional mitochondrial enzyme. Case presentation: We report our 4-year-old Saudi boy of non-consanguineous parents, with a compound heterozygous mutation in KARS1 gene presenting clinically with speech delay, bilateral sensonural hearing loss, unilateral progressive hemiparesis, iron deficiency anemia and lytic bone lesions. Conclusion: KARS1 mutation has a heterogenous phenotypic presentation, and variable clinical severity. We report a new clinical feature of lytic bone lesions which could potentially expand the phenotype of this genetic disorder spectrum. Early recognition of the clinical presentation is warranted to facilitate diagnosis, prognosis and appropriate family counseling.