ABSTRACT
Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty and considerable psychosocial challenges. Semi-structured interviews (N = 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N = 11) and maternal (N = 13) perspectives were obtained, and thematic analysis was performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied, with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.
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.
