Correspondence on “Aminoacyl-tRNA synthetase deficiencies in search of common themes” by Fuchs et al.

A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders

“…No specific antiepileptic strategy has been highlighted as particular efficacious in previously reported QARS1 encephalopathy cases apart from one report of benefit from the ketogenic diet in a severe, early onset case with multi-drug resistant epilepsy [6]. New research suggests supplementation of the deficient amino acid in aaRS deficiencies may be beneficial [7], although oral glutamine supplementation has been reported to worsen seizure control in one QARS1 patient, for whom memantine was subsequently effective [2].…”

“…Another patient was homozygous for p.(Arg378His) but had no seizures. Five reported cases of QARS1 without epilepsy had homozygous missense mutations in the catalytic domain [2]. Functional testing of the QARS1 variants in most prior reports have noted either complete disruption or marked reduction of glutamine aminoacylation activity as well as reduced solubility of QARS protein with preserved protein expression, thus implying an adverse impact on protein folding and aggregation [4,6].…”

“…Variants in QARS1, inherited as an autosomal recessive disorder, have been associated with a syndrome of "Microcephaly, progressive, with seizures and cerebral and cerebellar atrophy" (OMIM #615760). At the time of this publication, variants in QARS1 (encoding glutaminyl-tRNA synthetase) were reported in 25 cases [1,2] with epilepsy affecting 86% including severe early infantile developmental and epileptic encephalopathy (DEE) and epilepsy of infancy with migrating focal seizures (EIMFS). 79% of reported QARS1-related epilepsy (15 of 19) are described as being pharmaco-resistant.…”

Correspondence on “Treatment of ARS deficiencies with specific amino acids” by Kok et al

“…Supplement of glutamine would possibly aggravate the extremely intractable seizures in GlnRS deficiency (glutamic acid and glutamine are excitatory neurotransmitters). 7,8 More understanding of the functions of human MSC might possibly help us develop new treatments for GlnRS deficiency.…”