Biochemical and genetic analysis of 3-methylglutaconic aciduria type IV: a diagnostic strategy
| Autor: | Richard J. Rodenburg, Katrin Heldt, Udo Wendel, An I. Jonckheere, Marjan Huizing, Lambert P. van den Heuvel, Saskia B. Wortmann, Ron A. Wevers, Udo F. H. Engelke, Leo A. J. Kluijtmans, Maaike de Vries, Jan A.M. Smeitink, Eva Morava |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Mitochondrial encephalomyopathy
Male Pathology medicine.medical_specialty Magnetic Resonance Spectroscopy Mitochondrial Diseases Energy and redox metabolism [NCMLS 4] SUCLA2 Respiratory chain Methylmalonic acidemia DNA-Directed DNA Polymerase Biology Genomic disorders and inherited multi-system disorders [IGMD 3] Glutarates Mitochondrial Proteins Mitochondrial myopathy Translational research [ONCOL 3] medicine Humans Adenosine Triphosphatases Infant Newborn Brain Brain Diseases Metabolic Inborn Facies Membrane Proteins Ryanodine Receptor Calcium Release Channel 3-Methylglutaconic Aciduria Mitochondrial Proton-Translocating ATPases medicine.disease Magnetic Resonance Imaging DNA Polymerase gamma Mitochondrial medicine [IGMD 8] Phenotype Methylmalonic aciduria Mutation Female Neurology (clinical) Cardiomyopathies Carrier Proteins Functional Neurogenomics [DCN 2] Central core disease Metabolism Inborn Errors |
| Zdroj: | Brain, 132, Pt 1, pp. 136-46 Brain, 132, 136-46 |
| ISSN: | 0006-8950 |
| DOI: | 10.1093/brain/awn296 |
| Popis: | Contains fulltext : 80489.pdf (Publisher’s version ) (Closed access) The heterogeneous group of 3-methylglutaconic aciduria type IV consists of patients with various organ involvement and mostly progressive neurological impairment in combination with 3-methylglutaconic aciduria and biochemical features of dysfunctional oxidative phosphorylation. Here we describe the clinical and biochemical phenotype in 18 children and define 4 clinical subgroups (encephalomyopathic, hepatocerebral, cardiomyopathic, myopathic). In the encephalomyopathic group with neurodegenerative symptoms and respiratory chain complex I deficiency, two of the children, presenting with mild Methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness, harboured SUCLA2 mutations. In children with a hepatocerebral phenotype most patients presented with complex I deficiency and mtDNA-depletion, three of which carried POLG1-mutations. In the cardiomyopathic subgroup most patients had complex V deficiency and an overlapping phenotype with that previously described in isolated complex V deficiency, in three patients a TMEM70 mutation was confirmed. In one male with a pure myopathic form and severe combined respiratory chain disorder, based on the pathogenomic histology of central core disease, RYR1 mutations were detected. In our patient group the presence of the biochemical marker 3-methylglutaconic acid was indicative for nuclear coded respiratory chain disorders. By delineating patient-groups we elucidated the genetic defect in 10 out of 18 children. Depending on the clinical and biochemical phenotype we suggest POLG1, SUCLA2, TMEM70 and RYR1 sequence analysis and mtDNA-depletion studies in children with 3-methylglutaconic aciduria type IV. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|