Elevated levels of BDNF and cathepsin-d as possible peripheral markers of neurodegeneration in plasma of patients with glutaric acidemia type I.

Abstract

Glutaric acidemia type I (GA1) is caused by severe deficiency of glutaryl-CoA dehydrogenase activity, resulting in an accumulation of glutaric acid and glutarylcarnitine (C5DC) in the organism. Patients affected by GA1 are asymptomatic in the neonate period but usually manifest chronically progressive neurodegeneration apart from severe encephalopathic crises associated with acute striatum necrosis. Neurological manifestations like dyskinesia, dystonia, hypotonia, muscle stiffness, and spasticity are present. Treatment is based on protein/lysine restriction and l-carnitine supplementation. In this work, we evaluated markers of neurodegeneration and inflammation, namely BDNF (brain-derived neurotrophic factor), NCAM (neuronal adhesion molecule), PDGF-AA (platelet-derived growth factor), and cathepsin-d in plasma of six treated GA1 patients. We first found marked increases of plasma C5DC concentrations in GA1 patients, as well as increased levels of the markers BDNF and cathepsin-d as compared to those of age-matched healthy children. Furthermore, C5DC concentrations were highly correlated with the levels of cathepsin-d. These results may demonstrate that brain tissue degeneration is present in GA1 patients and that there is a relationship between increased metabolites concentrations with this process. To the best of our knowledge, this is so far the first study showing altered peripheral parameters of neurodegeneration and inflammation in GA1 patients.

• Authors: Gilian Guerreiro, Carlos Eduardo Diaz Jaques, Moacir Wajner, Carmen Regla Vargas
• Journal: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience (Int J Dev Neurosci) Vol. 80 Issue 1 Pg. 42-49 (Feb 2020) ISSN: 1873-474X [Electronic] United States
• PMID: 31910296 (Publication Type: Journal Article)
• Copyright: © 2020 International Society for Developmental Neuroscience.

Chemical References

• Biomarkers
• Brain-Derived Neurotrophic Factor
• Neural Cell Adhesion Molecules
• Platelet-Derived Growth Factor
• platelet-derived growth factor A
• Glutaryl-CoA Dehydrogenase
• Cathepsin D

Topics

• Amino Acid Metabolism, Inborn Errors (blood, complications)
• Biomarkers (blood)
• Brain Diseases, Metabolic (blood, complications)
• Brain-Derived Neurotrophic Factor (blood)
• Cathepsin D (blood)
• Child
• Child, Preschool
• Female
• Glutaryl-CoA Dehydrogenase (blood, deficiency)
• Humans
• Infant
• Infant, Newborn
• Male
• Nerve Degeneration (blood, diagnosis, etiology)
• Neural Cell Adhesion Molecules (blood)
• Platelet-Derived Growth Factor (metabolism)