Dokument: Tyrosine supplementation with high-protein diet as a therapeutic strategy for YARS1 deficiency
| Titel: | Tyrosine supplementation with high-protein diet as a therapeutic strategy for YARS1 deficiency | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=72489 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20260309-123945-3 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Averdunk, Luisa [Autor] Nunez Duran, Pedro Arsenio [Autor] Mayatepek, Ertan [Autor] Distelmaier, Felix [Autor] Lücke, Thomas [Autor] Konzett, Karin [Autor] Mandel, Hanna [Autor] Linden, Tobias [Autor] Neveu, Julien [Autor] Rohrlich, Pierre [Autor] | |||||||
| Dateien: |
| |||||||
| Stichwörter: | Amino acid supplementation , TyrRS , YARS1 , Aminoacyl-tRNA synthetase | |||||||
| Beschreibung: | 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. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Averdunk, L., Konzett, K., Mandel, H., Linden, T., Neveu, J., Rohrlich, P., Herrmann, M., Lücke, T., Hoffjan, S., Nunez Duran, P. A., Samra, N. N., Rudnik, S., Smith, D. E. C., Mayatepek, E., Salomons, G. S., Distelmaier, F., Mendes, M. I., & Lücke, T. (2026). Tyrosine supplementation with high-protein diet as a therapeutic strategy for YARS1 deficiency. Genetics in Medicine, 28(4), Article 101682. https://doi.org/10.1016/j.gim.2025.101682 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 09.03.2026 | |||||||
| Dateien geändert am: | 09.03.2026 |
