Alice Brambilla1, Silvia Favilli2, Iacopo Olivotto3, Giovanni Battista Calabri4, Giulio Porcedda4, Luciano De Simone5, Elena Procopio6, Elisabetta Pasquini7, Maria Alice Donati8. 1. University of Florence, Anna Meyer Children's Hospital, viale Pieraccini 24, 50139 Florence, Italy. Electronic address: alice.brambilla@unifi.it. 2. Paediatric Cardiology Unit, Anna Meyer Children's Hospital, viale Pieraccini 24, 50139 Florence, Italy. Electronic address: s.favilli@meyer.it. 3. Cardiomyopathy Unit, Careggi Hospital, Largo Brambilla 3, Florence, Italy. 4. Paediatric Cardiology Unit, Anna Meyer Children's Hospital, viale Pieraccini 24, 50139 Florence, Italy. 5. Paediatric Cardiology Unit, Anna Meyer Children's Hospital, viale Pieraccini 24, 50139 Florence, Italy. Electronic address: l.desimone@meyer.it. 6. Department of Inherited Neuro-metabolic Disorders, Anna Meyer Children's Hospital, viale Pieraccini 24, 50159 Florence, Italy. Electronic address: e.procopio@meyer.it. 7. Department of Inherited Neuro-metabolic Disorders, Anna Meyer Children's Hospital, viale Pieraccini 24, 50159 Florence, Italy. Electronic address: e.pasquini@meyer.it. 8. Department of Inherited Neuro-metabolic Disorders, Anna Meyer Children's Hospital, viale Pieraccini 24, 50159 Florence, Italy. Electronic address: maria.donati@meyer.it.
Abstract
BACKGROUND: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like (MELAS) syndrome is a rare condition with heterogeneous clinical presentation. Cardiac involvement commonly develops during adulthood, comprising both structural and conduction/arrhythmic abnormalities; early paediatric onset has rarely been reported. We describe the clinical profile, outcome and clinical implication of MELAS-associated cardiomyopathy at a tertiary referral centre. METHODS: From 2000 to 2016 we enrolled 21 patients affected by genetically-proven MELAS. Patients were followed-up at least annually over a mean of 8.5 years. RESULTS: All patients carried the MT-TL1 3243A>G mutation. Cardiac involvement was documented in 8 (38%) patients (three <18 years; five ≥18 years), including 6 (75%) with hypertrophic cardiomyopathy, 1 (12.5%) with dilated cardiomyopathy, and 1 (12.5%) with persistent pulmonary hypertension. During follow-up, 3 patients died, all with cardiac onset <18 years. The cause of death, however, was non-cardiac (infections, respiratory failure, stroke). Neither events nor cardiac progression were recorded among patients with onset ≥18 years. Adult cardiologists were responsible for 5/8 of referrals, even in patients with long-standing extra-cardiac involvement. CONCLUSIONS: Cardiac involvement was found in over 1/3 of patients with MELAS syndrome, and exhibited a bimodal age-related distribution with distinct final outcomes. Paediatric-onset cardiomyopathy represented a hallmark of systemic disease severity, without being the main determinant of outcome. Conversely, adult-onset cardiomyopathy appeared to represent a mild and non-progressive mid-term manifestation. Adult cardiologists played an important role in the diagnostic process, triggering suspicion of MELAS in most of patients diagnosis >18 years.
BACKGROUND: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like (MELAS) syndrome is a rare condition with heterogeneous clinical presentation. Cardiac involvement commonly develops during adulthood, comprising both structural and conduction/arrhythmic abnormalities; early paediatric onset has rarely been reported. We describe the clinical profile, outcome and clinical implication of MELAS-associated cardiomyopathy at a tertiary referral centre. METHODS: From 2000 to 2016 we enrolled 21 patients affected by genetically-proven MELAS. Patients were followed-up at least annually over a mean of 8.5 years. RESULTS: All patients carried the MT-TL1 3243A>G mutation. Cardiac involvement was documented in 8 (38%) patients (three <18 years; five ≥18 years), including 6 (75%) with hypertrophic cardiomyopathy, 1 (12.5%) with dilated cardiomyopathy, and 1 (12.5%) with persistent pulmonary hypertension. During follow-up, 3 patients died, all with cardiac onset <18 years. The cause of death, however, was non-cardiac (infections, respiratory failure, stroke). Neither events nor cardiac progression were recorded among patients with onset ≥18 years. Adult cardiologists were responsible for 5/8 of referrals, even in patients with long-standing extra-cardiac involvement. CONCLUSIONS:Cardiac involvement was found in over 1/3 of patients with MELAS syndrome, and exhibited a bimodal age-related distribution with distinct final outcomes. Paediatric-onset cardiomyopathy represented a hallmark of systemic disease severity, without being the main determinant of outcome. Conversely, adult-onset cardiomyopathy appeared to represent a mild and non-progressive mid-term manifestation. Adult cardiologists played an important role in the diagnostic process, triggering suspicion of MELAS in most of patients diagnosis >18 years.
Authors: Emanuele Monda; Marta Rubino; Michele Lioncino; Francesco Di Fraia; Roberta Pacileo; Federica Verrillo; Annapaola Cirillo; Martina Caiazza; Adelaide Fusco; Augusto Esposito; Fabio Fimiani; Giuseppe Palmiero; Giuseppe Pacileo; Paolo Calabrò; Maria Giovanna Russo; Giuseppe Limongelli Journal: Front Pediatr Date: 2021-02-25 Impact factor: 3.569