ReviewJournal of inherited metabolic disease2004
Vascular dysfunction as an additional pathomechanism in glutaric aciduria type I.
Review in Journal of inherited metabolic disease, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Rescue of glutaric aciduria type I in mice by liver-directed therapies.Science translational medicine · 2023Article
- Lipopolysaccharide-Elicited Systemic Inflammation Induces Selective Vulnerability of Cerebral Cortex and Striatum of Developing Glutaryl-CoA Dehydrogenase Deficient (GcdhNeurotoxicity research · 2020Article
- Glutaric Acid Affects Pericyte Contractility and Migration: Possible Implications for GA-I Pathogenesis.Molecular neurobiology · 2019Article
- Neurological manifestations of organic acidurias.Nature reviews. Neurology · 2019Review
- Two Uneventful Pregnancies in a Woman with Glutaric Aciduria Type 1.JIMD reports · 2018Article
- Diagnosis and Genetic Analysis of Glutaric Acidaemia Type I: Very rarely seen inborn error of metabolism.Sultan Qaboos University medical journal · 2015Article
- Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I.Acta neuropathologica communications · 2014Article
- Increased blood-brain barrier permeability and alterations in perivascular astrocytes and pericytes induced by intracisternal glutaric acid.Fluids and barriers of the CNS · 2014Article
- Caspase-3 mediates apoptosis of striatal cells in GA I rat model.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2012Article
- Outcome of three cases of untreated maternal glutaric aciduria type I.European journal of pediatrics · 2008Article
- Glutaric acidemia type 1.American journal of medical genetics. Part C, Seminars in medical genetics · 2006Review
- Glutaric acid administration impairs energy metabolism in midbrain and skeletal muscle of young rats.Neurochemical research · 2005Article
- Challenges for basic research in glutaryl-CoA dehydrogenase deficiency.Journal of inherited metabolic disease · 2004Review
- Emergency treatment in glutaryl-CoA dehydrogenase deficiency.Journal of inherited metabolic disease · 2004Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The metabolic hallmark of glutaric aciduria type I (GA I) is the deficiency of glutaryl-CoA dehydrogenase (GCDH) with subsequent accumulation of glutaric acid, 3-hydroxglutaric acid (3-OH-GA) and glutaconic acid. Current concepts regarding pathomechanisms of GA I focus on investigations of excitotoxic effects of 3-OH-GA. To identify pathogenetically relevant genes, microarray analyses were performed using brain material from GCDH-deficient (GCDH (-/-)) and control mice. These microarray data confirmed recent pathogenic models, but also revealed alterations in genes that had previously not been correlated to the disease, e.g. genes concerning vascular biology. Subsequent in vitro and in vivo experiments confirmed direct effects of 3-OH-GA on vascular permeability and endothelial integrity. Clinical observations underscore the involvement of vascular dysfunction. In MRI scans of GA I patients, subdural effusions as well as dilated transarachnoid vascular plexuses were detected independently of encephalopathic crises. In fact, some of these findings are already detectable shortly after birth. MRI scans of a GA I patient performed during an acute encephalopathic crisis detected a dilated intrastriatal vasculature with perivascular hyperintensity, indicating local extravasation. In conclusion, we hypothesize that 3-OH-GA affects prenatal development of vessels, thus leading to an increased vulnerability of endothelial structures and subsequent vascular dysfunction. These observations display an additional pathomechanism in GA I and might explain frontotemporal hypoplasia and chronic subdural effusions in this disease. Elucidation of the pathomechanisms of vascular dysfunction may give further insights into the pathogenesis of GA I.
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