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DOI: 10.1055/a-2008-4230
Treatment of Mitochondrial Phenylalanyl-tRNa-Synthetase Deficiency (FARS2) with Oral Phenylalanine
Funding This work was supported by ERAPERMED2019-310—Personalized Mitochondrial Medicine (PerMiM): Optimizing diagnostics and treatment for patients with mitochondrial diseases (FWF 4704-B) to SBW, and the European Joint Programme on Rare Diseases, EJPRD19-145 GENOMIT I4695-B project financed by the Austrian Science Funds (FWF) to JAM.![](https://www.thieme-connect.de/media/neuropediatrics/202305/lookinside/thumbnails/10-1055-a-2008-4230_1220223375sc-1.jpg)
Abstract
Objective By loading transfer RNAs with their cognate amino acids, aminoacyl-tRNA synthetases (ARS) are essential for protein translation. Both cytosolic ARS1-deficiencies and mitochondrial ARS2 deficiencies can cause severe diseases. Amino acid supplementation has shown to positively influence the clinical course of four individuals with cytosolic ARS1 deficiencies. We hypothesize that this intervention could also benefit individuals with mitochondrial ARS2 deficiencies.
Methods This study was designed as a N-of-1 trial. Daily oral L-phenylalanine supplementation was used in a 3-year-old girl with FARS2 deficiency. A period without supplementation was implemented to discriminate the effects of treatment from age-related developments and continuing physiotherapy. Treatment effects were measured through a physiotherapeutic testing battery, including movement assessment battery for children, dynamic gait index, gross motor function measure 66, and quality of life questionnaires.
Results The individual showed clear improvement in all areas tested, especially in gross motor skills, movement abilities, and postural stability. In the period without supplementation, she lost newly acquired motor skills but regained these upon restarting supplementation. No adverse effects and good tolerance of treatment were observed.
Interpretation and Conclusion Our positive results encourage further studies both on L-phenylalanine for other individuals with FARS2 deficiency and the exploration of this treatment rationale for other ARS2 deficiencies. Additionally, treatment costs were relatively low at 1.10 €/day.
Keywords
aminoacyl-tRNA-synthetase - individual treatment - ataxia - mitochondrial disorder - mitochondrial diseasesAuthors' Contributions
S.L.O., K.S., M.T.A., E.G., R.E.B., W.M.S., E.T., E.H., A.E., D.M., and J.A.M. made substantial contributions to acquisition, analysis, or interpretation of data for the work and drafted the work. SBW conceptualized and designed the study and contributed substantially to acquisition and analysis of data, drafting a significant portion of the manuscript or figures.
All authors revising it critically for important intellectual content and approved the final version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
* These authors contributed equally.
Publication History
Received: 01 December 2022
Accepted: 04 January 2023
Accepted Manuscript online:
05 January 2023
Article published online:
20 February 2023
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