Isolated methylmalonic aciduria (MMA) is an autosomal-recessive disorder of propionate metabolism that is most commonly caused by mutations in the methylmalonyl-CoA mutase (MUT) gene (mut-type MMA). We investigated a cohort of 151 patients, classifying 114 patients as mut(0) and 32 as mut(-) (five not defined). As per the definition, mut(-) patients showed a higher propionate incorporation ratio in vitro, which was correlated to a considerably later age of onset compared with mut(0) patients. In all patients, we found a total of 110 different mutations, of which 41 were novel. While the missense alleles p.Asn219Tyr, p.Arg369His, and p.Arg694Trp recurred in >10 alleles, 47 mutations were identified only once, suggesting many patients carry private mutations. Deficient alleles in the mut(-) subclass were almost exclusively caused by missense mutations, found disproportionately in the C-terminal cofactor binding domain. On the contrary, only half of the mut(0) mutations were of the missense type. Western blot analysis revealed reduced MUT protein for all 34 cell lines (27 mut(0) , seven mut(-) ) tested, suggesting protein instability as a major mechanism of deficiency in mut-type MMA. This large-scale evaluation helps to characterize the landscape of MUT mutations and their relationship to dysfunction and disease.

This study compares the impact of children’s cardiac rhythm devices and health status on their parents with that of healthy controls. Furthermore, it aims to ascertain whether sociodemographic characteristics and medical data are associated with parent-reported impacts. This cross-sectional study is part of a comprehensive single-center study of long-term psychosocial outcomes in pediatric patients with pacemakers and implantable cardioverter defibrillators. The study includes 69 patients with their parents: 69 mothers and 57 fathers. Parents responded to the Pediatric Quality of Life Inventory Family Impact Module and to open-ended questions assessing impact on family life and treatment satisfaction. Parents reported more negative impact on family life than healthy controls in all three summary scores. Among fathers, presence of a child’s congenital heart disease and female sex is associated with lower family function. No group differences emerged regarding device type. Positive and negative cognitive aspects predominated for patients’ mothers and fathers. However, one substantial difference is that mothers reported more positive and negative emotional impact than fathers. We conclude that parents’ well-being should be addressed in clinical contexts, especially through emotional and practical support and open communication focused on parents’ worries and concerns.