Leukoencephalopathy with thalamus and brainstem involvement and high lactate 'LTBL' caused by EARS2 mutations
| Autor: | Holger Prokisch, Daniele Ghezzi, Eugenio Grillo, Carola G.M. van Berkel, Truus E.M. Abbink, Marjo S. van der Knaap, Johann te Water Naude, Tobias B. Haack, Luísa Diogo, Diego Martinelli, Marjan E. Steenweg, Massimo Zeviani, Annette Bley, Tim M. Strom, Enrico Bertini |
|---|---|
| Přispěvatelé: | Neurology, Pediatric surgery, NCA - Childhood White Matter Diseases, Neuroscience Campus Amsterdam - Childhood White Matter Diseases |
| Rok vydání: | 2012 |
| Předmět: |
Male
leukoencephalopathy Pathology medicine.medical_specialty Cerebellum Magnetic Resonance Spectroscopy Cells Mitochondrial disease DNA Mutational Analysis Respiratory chain Biology Leukoencephalopathy White matter Mitochondrial Proteins Atrophy Oxygen Consumption SDG 3 - Good Health and Well-being Thalamus Leukoencephalopathies medicine Humans Lactic Acid Child Cells Cultured Skin Cultured medicine.diagnostic_test Magnetic resonance imaging mitochondrial DNA translation Fibroblasts medicine.disease Magnetic Resonance Imaging mitochondrial disease Glutamate-tRNA Ligase medicine.anatomical_structure Electron Transport Chain Complex Proteins Mutation mitochondrial aminoacyl-tRNA synthetase magnetic resonance imaging Brain Stem Female Protons Neurology (clinical) Brainstem human activities |
| Zdroj: | Brain, 135, 1387-1394. Oxford University Press Steenweg, M E, Ghezzi, D, Haack, T, Abbink, G E M, Martinelli, D, van Berkel, C G M, Bley, A, Diogo, L, Grillo, E, Naude, J T W, Strom, T M, Bertini, E, Prokisch, H, van der Knaap, M S & Zeviani, M 2012, ' Leukoencephalopathy with thalamus and brainstem involvement and high lactate 'LTBL' caused by EARS2 mutations ', Brain, vol. 135, pp. 1387-1394 . https://doi.org/10.1093/brain/aws070 |
| ISSN: | 1460-2156 0006-8950 |
| DOI: | 10.1093/brain/aws070 |
| Popis: | In the large group of genetically undetermined infantile-onset mitochondrial encephalopathies, multiple defects of mitochondrial DNA-related respiratory-chain complexes constitute a frequent biochemical signature. In order to identify responsible genes, we used exome-next-generation sequencing in a selected cohort of patients with this biochemical signature. In an isolated patient, we found two mutant alleles for EARS2, the gene encoding mitochondrial glutamyl-tRNA synthetase. The brain magnetic resonance imaging of this patient was hallmarked by extensive symmetrical cerebral white matter abnormalities sparing the periventricular rim and symmetrical signal abnormalities of the thalami, midbrain, pons, medulla oblongata and cerebellar white matter. Proton magnetic resonance spectroscopy showed increased lactate. We matched this magnetic resonance imaging pattern with that of a cohort of 11 previously selected unrelated cases. We found mutations in the EARS2 gene in all. Subsequent detailed clinical and magnetic resonance imaging based phenotyping revealed two distinct groups: mild and severe. All 12 patients shared an infantile onset and rapidly progressive disease with severe magnetic resonance imaging abnormalities and increased lactate in body fluids and proton magnetic resonance spectroscopy. Patients in the 'mild' group partially recovered and regained milestones in the following years with striking magnetic resonance imaging improvement and declining lactate levels, whereas those of the 'severe' group were characterized by clinical stagnation, brain atrophy on magnetic resonance imaging and persistent lactate increases. This new neurological disease, early-onset leukoencephalopathy with thalamus and brainstem involvement and high lactate, is hallmarked by unique magnetic resonance imaging features, defined by a peculiar biphasic clinical course and caused by mutations in a single gene, EARS2, expanding the list of medically relevant defects of mitochondrial DNA translation. © 2012 The Author. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|