Genetics in medicine : official journal of the American College of Medical Genetics · 2026
Tyrosine supplementation with high-protein diet as a therapeutic strategy for YARS1 deficiency.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Averdunk Luisa, Konzett Karin, Mandel Hanna, Linden Tobias, Neveu Julien, Rohrlich Pierre, Herrmann Melanie, Lücke Thomas, Hoffjan Sabine, Nunez Duran Pedro Arsenio, Samra Nadra Nasser, Rudnik Sabine, Smith Desiree E C, Mayatepek Ertan, Salomons Gajja S, Distelmaier Felix, Mendes Marisa I
Аннотация
PURPOSE: Biallelic pathogenic variants in YARS1 cause tyrosyl-tRNA synthase (TyrRS) deficiency that compromises the loading of tyrosine to its tRNA. YARS1 deficiency is characterized by impairment of neurological development, growth, liver function, and hematopoiesis. For other aminoacyl-tRNA synthetase deficiencies, supplementation of the respective amino acid and high-protein diet improved outcome. Whether tyrosine supplementation is effective in YARS1 deficiency is not known.
METHODS: Nine individuals with YARS1 deficiency received tyrosine (7 with and 2 without a high-protein diet). Aminoacylation was measured in patient-derived fibroblasts.
RESULTS: Since supplementation, cooperation, endurance, and motor skills improved in 8 of 9 children. Two children demonstrated significant progress in active language skills. Weight gain improved in 6 of 9, and vomiting stopped in all cases. In 4 of 9 children, hematological parameters improved. In vitro, the TyrRS activity determined in 3 fibroblast cell lines homozygous for p.(Arg367Trp) was significantly reduced (0%, 6%, and 24%) at 100 μM tyrosine (physiological blood concentration). At 500 μM tyrosine, TyrRS activity increased to almost normal activity relative to controls at 100 μM.
CONCLUSION: Given the positive cost/risk-benefit ratio, we advocate therapeutic trials with tyrosine supplementation and high-protein diet for YARS1 deficiency. Further studies should aim to determine variant-specific differences and long-term outcomes in comparison with natural history.
METHODS: Nine individuals with YARS1 deficiency received tyrosine (7 with and 2 without a high-protein diet). Aminoacylation was measured in patient-derived fibroblasts.
RESULTS: Since supplementation, cooperation, endurance, and motor skills improved in 8 of 9 children. Two children demonstrated significant progress in active language skills. Weight gain improved in 6 of 9, and vomiting stopped in all cases. In 4 of 9 children, hematological parameters improved. In vitro, the TyrRS activity determined in 3 fibroblast cell lines homozygous for p.(Arg367Trp) was significantly reduced (0%, 6%, and 24%) at 100 μM tyrosine (physiological blood concentration). At 500 μM tyrosine, TyrRS activity increased to almost normal activity relative to controls at 100 μM.
CONCLUSION: Given the positive cost/risk-benefit ratio, we advocate therapeutic trials with tyrosine supplementation and high-protein diet for YARS1 deficiency. Further studies should aim to determine variant-specific differences and long-term outcomes in comparison with natural history.