Cardiomyopathy in children with mitochondrial disease: Prognosis and genetic background.
Exome sequencing
Infantile cardiomyopathy
Mitochondrial cardiomyopathy
Mitochondrial disease
Mitochondrial respiratory chain complex deficiencies
Journal
International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291
Informations de publication
Date de publication:
15 Mar 2019
15 Mar 2019
Historique:
received:
10
07
2018
revised:
30
12
2018
accepted:
03
01
2019
pubmed:
16
1
2019
medline:
18
12
2019
entrez:
16
1
2019
Statut:
ppublish
Résumé
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. 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 < 0.001). Ten-year Kaplan-Meier estimates of overall survival were 18 and 67%, respectively. Among the 21 cardiomyopathy patients who died, two died within one month of birth (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). 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.
Sections du résumé
BACKGROUND
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
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 < 0.001). Ten-year Kaplan-Meier estimates of overall survival were 18 and 67%, respectively. Among the 21 cardiomyopathy patients who died, two died within one month of birth (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
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.
Identifiants
pubmed: 30642647
pii: S0167-5273(18)34315-8
doi: 10.1016/j.ijcard.2019.01.017
pii:
doi:
Substances chimiques
DNA, Mitochondrial
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
115-121Informations de copyright
Copyright © 2019. Published by Elsevier B.V.