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In\u2010vitro studies have previously shown that histidine can rescue a humanized yeast model for pathogenic HARS alleles. Fourteen children homozygous for HARS Y454S were treated with supplemental oral histidine (50 mg\/kg BID) and monitored with bloodwork and physical, visual, and audiometry assessments during a 3\u2010year clinical trial, then followed for more than 4\u2009years on histidine in the post\u2010trial period. Patient fibroblasts were assessed for response to histidine. Hearing and vision remained stable, and growth improved significantly. Children remained healthy, with no severe deteriorations despite exposure to bacterial and viral infections, including COVID\u201019. Gains in growth were maintained in the post\u2010trial period on varying levels of histidine supplementation. Daily oral histidine supplementation in children with autosomal recessive HARS1\u2010related disorder can ameliorate or slow the progression of disease and is safe, inexpensive, and well tolerated. This study adds to the growing list of autosomal recessive ARSopathies (aminoacyl\u2010tRNA synthetase disorders) that are amenable to amino acid supplementation.<\/jats:p>","DOI":"10.1002\/ajmg.a.70203","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:02:22Z","timestamp":1779249742000},"page":"2289-2308","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Histidine Supplementation Stabilizes Hearing and Vision and Improves Growth in\n                    <scp>HARS1<\/scp>\n                    \u2010Related Autosomal Recessive Disorder Associated With Usher\u2010Like Symptoms"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0151-8111","authenticated-orcid":false,"given":"Victoria Mok","family":"Siu","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Paediatrics Western University  London Ontario Canada"},{"name":"Children's Health Research Institute  London Ontario Canada"},{"name":"Medical Genetics Clinic, London Health Sciences Centre  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosan","family":"Kenana","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Medical Genetics Clinic, London Health Sciences Centre  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah D. 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