Journal of Clinical Medicine (Jan 2019)
Muscle Involvement in a Large Cohort of Pediatric Patients with Genetic Diagnosis of Mitochondrial Disease
- Cristina Jou,
- Juan D. Ortigoza-Escobar,
- Maria M. O’Callaghan,
- Andres Nascimento,
- Alejandra Darling,
- Leticia Pias-Peleteiro,
- Belén Perez-Dueñas,
- Mercedes Pineda,
- Anna Codina,
- César Arjona,
- Judith Armstrong,
- Francesc Palau,
- Antonia Ribes,
- Laura Gort,
- Frederic Tort,
- Placido Navas,
- Eduardo Ruiz-Pesini,
- Sonia Emperador,
- Ester Lopez-Gallardo,
- Pilar Bayona-Bafaluy,
- Raquel Montero,
- Cecilia Jimenez-Mallebrera,
- Angels Garcia-Cazorla,
- Julio Montoya,
- Delia Yubero,
- Rafael Artuch
Affiliations
- Cristina Jou
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Juan D. Ortigoza-Escobar
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Maria M. O’Callaghan
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Andres Nascimento
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Alejandra Darling
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Leticia Pias-Peleteiro
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Belén Perez-Dueñas
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Mercedes Pineda
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Anna Codina
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- César Arjona
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Judith Armstrong
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Francesc Palau
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Antonia Ribes
- Secció d’Errors Congènits del Metabolisme—IBC, Servei de Bioquímica i Genètica Molecular, Hospital Clínic, IDIBAPS, CIBERER-ISCIII, 08028 Barcelona, Spain
- Laura Gort
- Secció d’Errors Congènits del Metabolisme—IBC, Servei de Bioquímica i Genètica Molecular, Hospital Clínic, IDIBAPS, CIBERER-ISCIII, 08028 Barcelona, Spain
- Frederic Tort
- Secció d’Errors Congènits del Metabolisme—IBC, Servei de Bioquímica i Genètica Molecular, Hospital Clínic, IDIBAPS, CIBERER-ISCIII, 08028 Barcelona, Spain
- Placido Navas
- Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and CIBERER-ISCIII, 41013 Sevilla, Spain
- Eduardo Ruiz-Pesini
- Departamento de Bioquímica, Biología Molecular y Celular, Instituto de investigación Sanitaria de Aragón and CIBERER-ISCIII, Universidad de Zaragoza, 50013 Zaragoza, Spain
- Sonia Emperador
- Departamento de Bioquímica, Biología Molecular y Celular, Instituto de investigación Sanitaria de Aragón and CIBERER-ISCIII, Universidad de Zaragoza, 50013 Zaragoza, Spain
- Ester Lopez-Gallardo
- Departamento de Bioquímica, Biología Molecular y Celular, Instituto de investigación Sanitaria de Aragón and CIBERER-ISCIII, Universidad de Zaragoza, 50013 Zaragoza, Spain
- Pilar Bayona-Bafaluy
- Departamento de Bioquímica, Biología Molecular y Celular, Instituto de investigación Sanitaria de Aragón and CIBERER-ISCIII, Universidad de Zaragoza, 50013 Zaragoza, Spain
- Raquel Montero
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Cecilia Jimenez-Mallebrera
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Angels Garcia-Cazorla
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Julio Montoya
- Departamento de Bioquímica, Biología Molecular y Celular, Instituto de investigación Sanitaria de Aragón and CIBERER-ISCIII, Universidad de Zaragoza, 50013 Zaragoza, Spain
- Delia Yubero
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- Rafael Artuch
- Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, 08950 Esplugues, Spain
- DOI
- https://doi.org/10.3390/jcm8010068
- Journal volume & issue
-
Vol. 8,
no. 1
p. 68
Abstract
Mitochondrial diseases (MD) are a group of genetic and acquired disorders which present significant diagnostic challenges. Here we report the disease characteristics of a large cohort of pediatric MD patients (n = 95) with a definitive genetic diagnosis, giving special emphasis on clinical muscle involvement, biochemical and histopathological features. Of the whole cohort, 51 patients harbored mutations in nuclear DNA (nDNA) genes and 44 patients had mutations in mitochondrial DNA (mtDNA) genes. The nDNA patients were more likely to have a reduction in muscle fiber succinate dehydrogenase (SDH) stains and in SDH-positive blood vessels, while a higher frequency of mtDNA patients had ragged red (RRF) and blue fibers. The presence of positive histopathological features was associated with ophthalmoplegia, myopathic facies, weakness and exercise intolerance. In 17 patients younger than two years of age, RRF and blue fibers were observed only in one case, six cases presented cytochrome c oxidase (COX) reduction/COX-fibers, SDH reduction was observed in five and all except one presented SDH-positive blood vessels. In conclusion, muscle involvement was a frequent finding in our series of MD patients, especially in those harboring mutations in mtDNA genes.
Keywords
- mitochondrial diseases
- myopathy
- pediatric patients
- biochemical markers
- muscle histopathology
- next generation sequencing