Histidine Supplementation Stabilizes Hearing and Vision and Improves Growth in HARS1-Related Autosomal Recessive Disorder Associated With Usher-Like Symptoms

Homozygous HARS1 Y454S variant → histidyl-tRNA synthetase deficiency → impaired mitochondrial translation → progressive hearing, vision, and respiratory deterioration

A clinical trial in 14 children homozygous for the HARS1 Y454S variant demonstrates that oral histidine supplementation (50 mg/kg twice daily) stabilizes hearing and vision and significantly improves growth over more than 4 years of follow-up. This inexpensive, well-tolerated treatment adds to the growing list of ARSopathies amenable to cognate amino acid supplementation. Patient fibroblasts also showed in vitro response to histidine, reinforcing the proposed mechanism of action.

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

This result is particularly striking in rare genetics: a simple, inexpensive, accessible treatment that stabilizes an otherwise progressive disease toward deafness, blindness, and risk of sudden death. The principle — supplementing the cognate amino acid to compensate for reduced synthetase activity — opens a therapeutic avenue for other ARSopathies still without treatment, and warrants evaluation in a controlled trial.

Clinical impact: 3/3 · Evidence strength: 1/3 · Novelty: 2/2 · Sample size: 1/1 · Journal quality: 1/1 → Total: 8/10