Neurodegenerative biomarkers and inflammation in patients with propionic and methylmalonic acidemias: effect of L-carnitine treatment

• Published in: Metabolic brain disease 2024-11, Vol.40 (1), p.6, Article 6
• Main Authors: dos Reis, Bianca Gomes, Becker, Graziela Schmitt, Marchetti, Desirèe Padilha, de Moura Coelho, Daniella, Sitta, Angela, Wajner, Moacir, Vargas, Carmen Regla
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Amino Acid Metabolism, Inborn Errors - blood; Amino Acid Metabolism, Inborn Errors - drug therapy; Biochemistry; Biomarkers; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Biomolecules; Brain-derived neurotrophic factor; C-reactive protein; C-Reactive Protein - analysis; C-Reactive Protein - metabolism; Carnitine; Carnitine - therapeutic use; Child; Child, Preschool; Cytokines - blood; Dietary restrictions; Female; Genetic disorders; Humans; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Interleukin 10; Male; Metabolic Diseases; Metabolites; Neural cell adhesion molecule; Neurodegeneration; Neurodegenerative Diseases - blood; Neurodegenerative Diseases - drug therapy; Neurological complications; Neurological diseases; Neurology; Neurosciences; Nutrient deficiency; Oncology; Oxidation; Oxidative Stress - drug effects; Propionic Acidemia - drug therapy; Proteins; Thiobarbituric acid; Tumor necrosis factor-α
• ISSN: 1573-7365; 0885-7490; 1573-7365
• DOI: 10.1007/s11011-024-01475-9

Propionic and methylmalonic acidemias (PAcidemia and MMAcidemia, respectively) are genetic disorders characterized by acute metabolic decompensation and neurological complications. L-carnitine (LC) is effective in reducing toxic metabolites that are related to the pathophysiology of these diseases. Therefore we investigated biomarkers of inflammation (cytokines and C-reactive protein (CRP)), neurodegeneration (BDNF, NCAM-1 and cathepsin-D) and biomolecules oxidation (sulfhydryl content and thiobarbituric acid-reactive species (TBARS)), as well as carnitine concentrations in untreated patients with PAcidemia and MMAcidemia, in patients under treatment with LC and a protein-restricted diet for until 2 years and in patients under the same treatment for more than 2 years. It was verified an increase of CRP, IL-6, IL-8, TNF-α, IL-10, NCAM-1 and cathepsin-D in untreated patients compared to controls. On the other hand, reduced levels of TNF-α, CRP, IL-10, NCAM-1 and cathepsin-D were found in plasma from treated patients, as well as increased concentrations of LC. Furthermore, oxidative biomarkers were increased in untreated patients and were normalized with the prolonged treatment with LC. In conclusion, this work shows, for the first time, that inflammatory and neurodegenerative peripheral biomarkers are increased in patients with PAcidemia and MMAcidemia and that treatment with LC is effective to protect against these alterations.