Nicotinamide Riboside for Ataxia Telangiectasia: A Report of an Early Treated Individual.

A first study on nicotinamide riboside treatment of 24 individuals with ataxia telangiectasia with a mean age of 17.5 years showed improved ataxia scores and immunoglobulin levels. We here present the effect of nicotinamide riboside in another individual with ataxia and recurrent infections in whom treatment started as early as at the age of 3 years and 6 months.During 11 months of follow-up, mean total Scale-for-the-Assessment-and-Rating-of-Ataxia decreased from 27 to 9 points and mean total Score for the Gross-Motor-Function-Measure increased from 61 to 78%. Improvement in drawing skills was observed by ICF-based ergotherapeutic examination. Use of antibiotics and frequency of hospitalizations due to infections were reduced by more than 90%. Immunological parameters in blood remained unchanged. No adverse effects occurred.While the effects on motor and speech improvement might be partly explained by development, our study replicates the previous finding of a positive effect of nicotinamide riboside treatment in ataxia telangiectasia. One could even hypothesize that the early treatment will lead to even better outcome. Given the absence of adverse effects, we strongly encourage to consider nicotinamide riboside in all individuals with ataxia telangiectasia.

Treatment of Mitochondrial Phenylalanyl-tRNa-Synthetase Deficiency (FARS2) with Oral Phenylalanine.

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.