Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases
Abstract Background Leigh syndrome (LS) is a progressive neurodegenerative disorder associated with primary or secondary dysfunction of mitochondrial oxidative phosphorylation and is the most common mitochondrial disease in childhood. Numerous reports on the biochemical and molecular profiles of LS...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-021-02029-3 |
| _version_ | 1818367313025433600 |
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| author | Anna Ardissone Claudio Bruno Daria Diodato Alice Donati Daniele Ghezzi Eleonora Lamantea Costanza Lamperti Michelangelo Mancuso Diego Martinelli Guido Primiano Elena Procopio Anna Rubegni Filippo Santorelli Maria Cristina Schiaffino Serenella Servidei Flavia Tubili Enrico Bertini Isabella Moroni |
| author_facet | Anna Ardissone Claudio Bruno Daria Diodato Alice Donati Daniele Ghezzi Eleonora Lamantea Costanza Lamperti Michelangelo Mancuso Diego Martinelli Guido Primiano Elena Procopio Anna Rubegni Filippo Santorelli Maria Cristina Schiaffino Serenella Servidei Flavia Tubili Enrico Bertini Isabella Moroni |
| author_sort | Anna Ardissone |
| collection | DOAJ |
| description | Abstract Background Leigh syndrome (LS) is a progressive neurodegenerative disorder associated with primary or secondary dysfunction of mitochondrial oxidative phosphorylation and is the most common mitochondrial disease in childhood. Numerous reports on the biochemical and molecular profiles of LS have been published, but there are limited studies on genetically confirmed large series. We reviewed the clinical, imaging, biochemical and molecular data of 122 patients with a diagnosis of LS collected in the Italian Collaborative Network of Mitochondrial Diseases database. Results Clinical picture was characterized by early onset of several neurological signs dominated by central nervous system involvement associated with both supra- and sub-tentorial grey matter at MRI in the majority of cases. Extraneurological organ involvement is less frequent in LS than expected for a mitochondrial disorder. Complex I and IV deficiencies were the most common biochemical diagnoses, mostly associated with mutations in SURF1 or mitochondrial-DNA genes encoding complex I subunits. Our data showed SURF1 as the genotype with the most unfavorable prognosis, differently from other cohorts reported to date. Conclusion We report on a large genetically defined LS cohort, adding new data on phenotype-genotype correlation, prognostic factors and possible suggestions to diagnostic workup. |
| first_indexed | 2024-12-13T22:50:04Z |
| format | Article |
| id | doaj.art-5ccf0959ddf84ea0a5df4c99775bc8cc |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-13T22:50:04Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-5ccf0959ddf84ea0a5df4c99775bc8cc2022-12-21T23:28:39ZengBMCOrphanet Journal of Rare Diseases1750-11722021-10-0116111210.1186/s13023-021-02029-3Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseasesAnna Ardissone0Claudio Bruno1Daria Diodato2Alice Donati3Daniele Ghezzi4Eleonora Lamantea5Costanza Lamperti6Michelangelo Mancuso7Diego Martinelli8Guido Primiano9Elena Procopio10Anna Rubegni11Filippo Santorelli12Maria Cristina Schiaffino13Serenella Servidei14Flavia Tubili15Enrico Bertini16Isabella Moroni17Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico “Carlo Besta”Center of Translational and Experimental Myology, IRCCS Istituto Giannina GasliniMuscular and Neurodegenerative Disease Unit, Ospedale Pediatrico Bambino GesùMetabolic and Neuromuscular Unit, Meyer Children Hospital-University of FlorenceUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo BestaUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo BestaUnit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo BestaDepartment of Clinical and Experimental Medicine, Neurological Institute, University of PisaMetabolic Unit, Ospedale Pediatrico Bambino GesùUOC Neurofisiopatologia, Fondazione Policlinico Universitario A. Gemelli IRCCSMetabolic and Neuromuscular Unit, Meyer Children Hospital-University of FlorenceMolecular Medicine, IRCCS Fondazione Stella MarisMolecular Medicine, IRCCS Fondazione Stella MarisPediatric Clinic IRCCS Istituto Giannina GasliniUOC Neurofisiopatologia, Fondazione Policlinico Universitario A. Gemelli IRCCSMetabolic and Neuromuscular Unit, Meyer Children Hospital-University of FlorenceMuscular and Neurodegenerative Disease Unit, Ospedale Pediatrico Bambino GesùDepartment of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico “Carlo Besta”Abstract Background Leigh syndrome (LS) is a progressive neurodegenerative disorder associated with primary or secondary dysfunction of mitochondrial oxidative phosphorylation and is the most common mitochondrial disease in childhood. Numerous reports on the biochemical and molecular profiles of LS have been published, but there are limited studies on genetically confirmed large series. We reviewed the clinical, imaging, biochemical and molecular data of 122 patients with a diagnosis of LS collected in the Italian Collaborative Network of Mitochondrial Diseases database. Results Clinical picture was characterized by early onset of several neurological signs dominated by central nervous system involvement associated with both supra- and sub-tentorial grey matter at MRI in the majority of cases. Extraneurological organ involvement is less frequent in LS than expected for a mitochondrial disorder. Complex I and IV deficiencies were the most common biochemical diagnoses, mostly associated with mutations in SURF1 or mitochondrial-DNA genes encoding complex I subunits. Our data showed SURF1 as the genotype with the most unfavorable prognosis, differently from other cohorts reported to date. Conclusion We report on a large genetically defined LS cohort, adding new data on phenotype-genotype correlation, prognostic factors and possible suggestions to diagnostic workup.https://doi.org/10.1186/s13023-021-02029-3Leigh syndromeMitochondrial diseaseChildhoodBasal ganglia |
| spellingShingle | Anna Ardissone Claudio Bruno Daria Diodato Alice Donati Daniele Ghezzi Eleonora Lamantea Costanza Lamperti Michelangelo Mancuso Diego Martinelli Guido Primiano Elena Procopio Anna Rubegni Filippo Santorelli Maria Cristina Schiaffino Serenella Servidei Flavia Tubili Enrico Bertini Isabella Moroni Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases Orphanet Journal of Rare Diseases Leigh syndrome Mitochondrial disease Childhood Basal ganglia |
| title | Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases |
| title_full | Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases |
| title_fullStr | Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases |
| title_full_unstemmed | Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases |
| title_short | Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases |
| title_sort | clinical imaging biochemical and molecular features in leigh syndrome a study from the italian network of mitochondrial diseases |
| topic | Leigh syndrome Mitochondrial disease Childhood Basal ganglia |
| url | https://doi.org/10.1186/s13023-021-02029-3 |
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