Cardiomyopathy in children with mitochondrial disease: Prognosis and genetic background

Abstract Background Cardiomyopathy is a reported indicator of poor prognosis in children with mitochondrial disease. However, the association between prognosis and the genetic background of cardiomyopathy in children with mitochondrial disease has yet to be fully elucidated. Methods and results Of 137 children with mitochondrial disease whose genetic diagnosis was made between 2004 and 2018, 29 had mitochondrial cardiomyopathy (21%). After a median follow-up of 35 months, the overall survival rate was significantly lower in patients with cardiomyopathy than in those without (p  COQ4 in one patient, and COX10 in one patient), ten died within one year ( BOLA3 in three patients, QRSL1 in two patients, large chromosomal deletions in two patients, MT-ATP6/8 in one patient, MT-TL1 in one patient, and TAZ gene in one patient), and nine died after one year ( MT-ND5 in three patients, MT-TL1 in three patients, ACAD9 in one patient, KARS in one patient, and MT-TV in one patient). In the three patients with mitochondrial DNA mutations whose cardiac tissues were available, high heteroplasmy rates in the cardiac tissue were observed for m.8528T>C (90%, died at 2 months of age) and m.3243A>G (90 and 80%, died at 12 and 13 years of age, respectively). Conclusions In children with mitochondrial disease, cardiomyopathy was common (21%) and was associated with increased mortality. Genetic analysis coupled with detailed phenotyping could be useful for prognosis.