Aminoacyl-tRNA synthetases deficiency disorders: A case series in children

Introduction: Aminoacyl tRNA synthetases (AaRS) activate tRNA to aminoacyl tRNA which are essential for protein synthesis. Disorders in these proteins cause leucoencephaloapthies, hypomyelination, peripheral neuropathies and combined oxidative phosphorylation defects. Methods: Children with genetically confirmed AaRS gene mutations with matching phenotype were included in the study. Parental testing was done to confirm the mutations. Results: 10 children (6 boys, 4 girls) were included in the study: Two each with DARS and EARS mutations, one each with NARS2, TARS2, RARS2, AARS, and FARS2 mutations. Age of presentation ranged from 1 month to 5 years. Eight of 10 children were born to consanguineous parentage. Presenting complaints were developmental delay (DD) (3), seizures (3), DD with regression (2), walking difficulty (1), feeding difficulties and motor delay (1). Examination findings included central hypotonia (5), spastic diplegia (4), dystonia (2) and hypotonia with areflexia (1). The commonest neuroimaging abnormalities were hypomyelination (4), cerebrat atrophy (4), followed by vermian hypoplasia/atrophy (2), basal ganglia hyperintensities (1) with normal MRI in one child. On follow-up, 3 children died: all with severe epilepsy. Two children were lost to follow up. Of two children with EARS2, one child is currently normal, one child has DD and epilepsy. 3 children are non-ambulant with static course and no seizures. Conclusions: Common findings were developmental delay with or without regression, epilepsy and central hypotonia. Spastic diplegia and hypomyelination in MRI are strong pointers for these disorders. Epilepsy is a bad prognostic symptom.
Keywords: AaRS, Aminoacyl-tRNA synthesise, hypomyelination, hypotonia