Title Klinička, neuroslikovna i genetička obilježja pacijenata sa sindromom Leigh Title (english) Clinical, neuroimaging and genetic characteristics of a patient with Leigh syndrome Author Klara Miljanić Mentor Danijela Petković Ramadža (mentor)Committee member Ivo Barić (predsjednik povjerenstva)Committee member Marija Jelušić (član povjerenstva)Committee member Danijela Petković Ramadža (član povjerenstva)Granter University of Zagreb Defense date and country 2023-09-19, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract Sindrom Leigh je neurodegenerativna bolest uzrokovana smanjenom proizvodnjom energije u mitohondrijima, a nastaje zbog mutacija u jednom od preko 100 gena u nuklearnom ili mitohondrijskom genomu. Očituje se u ranom djetinjstvu subakutnom nekrotizirajućom encefalopatijom koju karakteriziraju poremećaj svijesti, psihomotorička regresija, distonija, bulbarna paraliza i zatajenje disanja. Meuroslikovno obilježje su obostrane simetrične lezije bazalnih ganglija, moždanog debla i malog mozga. Cilj ovog diplomskog rada bio je opisati klinička, neuroslikovna i genetička obilježja pacijenata sa sindromom Leigh liječenih u Zavodu za genetiku i bolesti metabolizma Klinike za pedijatriju KBC-a Zagreb u razdoblju od 2012. do 2022. godine. Ova retrospektivna studija uključila je 18 ispitanika s postavljenom dijagnozom sindroma Leigh. Kao izvori podataka korišteni su bolnička arhiva, bolnički informacijski sustav i ambulantni kartoni. Dijagnoza je postavljana na temelju kliničke slike, biokemijskih i neuroslikovnih nalaza, a u većine ispitanika je potvrđena genskom analizom. Medijan dobi pri postavljanju dijagnoze bio je 11 mjeseci. Kod 44,4 % pacijenata utvrđena je mutacija kod jednog ili oba roditelja. Najčešći provocirajući čimbenici bili su respiratorna infekcija i akutni gastroenterokolitis. / Najzastupljeniji — klinički znakovi encefalopatske krize bili su poremećaj svijesti, epileptički napadaji, malaksalost i hipotonija. Najznačajnija biokemijska obilježja su povišene koncentracije laktata i alanina u krvi i cerebrospinalnoj tekućini te patološko izlučivanje organskih kiselina urinom. Neuroslikovnom obradom nađeni su hiperintenziteti u T2/FLAIR mjerenim snimkama u području putamena, globusa palidusa, mezencefalona, ponsa i supkortikalne bijele tvari. Pacijenti su liječeni takozvanim mitohondrijskim koktelom (kombinacija koenzima Q: biotina, tiamina, riboflavina i antioksidansa, najčešće vitamina C). Palijativna skrb okosnica je skrbi o pacijentima sa sindromom Leigh. Pet pacijenata preminulo je od posljedica sindroma Leigh, a njih 13 ima teško psihomotoričko zaostajanje. Rezultati ove studije potvrđuju da je sindrom Leigh teška neurodegenerativna bolest koja dovodi do psihomotoričkog zaostajanja i prijevremene smrti.
Abstract (english) Leigh syndrome is a neurodegenerative disease caused by reduced energy production in the mitochondria, and is caused by mutations in one of over 100 genes in the nuclear or mitochondrial genome. It manifests itself in early childhood with subacute necrotizing encephalopathy characterized by impaired consciousness, psychomotor regression, dystonia, bulbar paralysis, and respiratory failure. The neuroimaging feature is bilateral symmetrical lesions of the basal ganglia, brainstem and cerebellum. The aim of this thesis was to describe the clinical, neuroimaging and genetic characteristics of patients with Leigh syndrome treated in the Department of Genetics and Metabolic Diseases of the Pediatric Clinic of University Hospital Centre Zagreb between 2012 and 2022. This retrospective study included 18 patients diagnosed with Leigh syndrome. The hospital archive, hospital information system and outpatient records were used as data sources. The diagnosis was established on the basis of the clinical picture, biochemical and neuroimaging findings, and in most subjects it was confirmed by genetic analysis. The median age at diagnosis was 11 months. In 44,4% of patients, a mutation was found in one or both parents. The most common provoking factors were respiratory infection and acute gastroenterocolitis. The most common clinical signs of encephalopathic crisis were loss of consciousness, epileptic seizures, weakness and hypotonia. The most significant biochemical features were increased concentrations of lactate and alanine in the blood and cerebrospinal fluid and pathological excretion of organic acids in the urine. Neuroimaging revealed hyperintensities in the T2/FLAIR weighted images in the area of the putamen, globus pallidus, mesencephalon, pons and subcortical white matter.
Patients were treated with the so-called mitochondrial cocktail (combination of coenzyme Q;,, biotin, thiamin, riboflavin and antioxidants, usually vitamin C). Palliative care is the backbone of care for patients with Leigh syndrome. Five patients died as a result of Leigh syndrome, and 13 showed signs of severe psychomotor retardation. The results of this study confirm that Leigh syndrome is a severe neurodegenerative disease that leads to psychomotor retardation and premature death.
Keywords
sindrom Leigh
mtDNA
heteroplazmija
subakutna nekrotizirajuća encefalopatija
bilateralni hiperintenziteti bazalnih ganglija
Keywords (english)
Leigh syndrome
mtDNA
heteroplasmy
subacute necrotizing encephalopathy
bilateral basal ganglia hyperintensities
Language croatian URN:NBN urn:nbn:hr:105:023199 Study programme Title: Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2023-10-26 12:31:29
