Mitochondrial aminoacyl-tRNA synthetase (ARS)-defects: a review of phenotypes and therapeutic strategies in 899 patients.

Systematic review of 899 patients with 19 types of mtARS deficiencies — HPO phenotypes, progression, mortality, and cognate amino acid supplementation

This scoping review identifies 899 patients with 19 different types of mitochondrial aminoacyl-tRNA synthetase (mtARS) deficiencies, with wide clinical variability: age of onset from 0 to 63 years, mortality from 0 to 57% depending on the type. Although neurological involvement is common, each mtARS deficiency has its own phenotypic signature. Cognate amino acid supplementation was explored in 11 patients with heterogeneous results, and remains to be evaluated in controlled trials.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This review comes at the right time, echoing the HARS1 trial published in the same issue. It confirms that mitochondrial ARSopathies are an important (899 published cases) but highly heterogeneous group, and that amino acid supplementation — though promising — remains insufficiently validated for most types. The HPO phenotypic framework provided will help harmonize phenotypes across centers.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 1/1 · Journal quality: 1/1 → Total: 7/10