PMID- 31910296
OWN - NLM
STAT- MEDLINE
DCOM- 20201118
LR  - 20201118
IS  - 1873-474X (Electronic)
IS  - 0736-5748 (Linking)
VI  - 80
IP  - 1
DP  - 2020 Feb
TI  - Elevated levels of BDNF and cathepsin-d as possible peripheral markers of 
      neurodegeneration in plasma of patients with glutaric acidemia type I.
PG  - 42-49
LID - 10.1002/jdn.10006 [doi]
AB  - 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.
CI  - (c) 2020 International Society for Developmental Neuroscience.
FAU - Guerreiro, Gilian
AU  - Guerreiro G
AUID- ORCID: 0000-0003-0380-4808
AD  - Faculdade de Farmacia, UFRGS, Porto Alegre, Brazil.
AD  - Servico de Genetica Medica, HCPA, UFRGS, Porto Alegre, Brazil.
FAU - Diaz Jaques, Carlos Eduardo
AU  - Diaz Jaques CE
AD  - Programa de Pos-Graduacao em CB:Bioquimica, UFRGS, Porto Alegre, Brazil.
FAU - Wajner, Moacir
AU  - Wajner M
AD  - Servico de Genetica Medica, HCPA, UFRGS, Porto Alegre, Brazil.
AD  - Programa de Pos-Graduacao em CB:Bioquimica, UFRGS, Porto Alegre, Brazil.
FAU - Vargas, Carmen Regla
AU  - Vargas CR
AD  - Faculdade de Farmacia, UFRGS, Porto Alegre, Brazil.
AD  - Servico de Genetica Medica, HCPA, UFRGS, Porto Alegre, Brazil.
AD  - Programa de Pos-Graduacao em CB:Bioquimica, UFRGS, Porto Alegre, Brazil.
AD  - Programa de Pos-Graduacao em Ciencias Farmaceuticas, UFRGS, Porto Alegre, Brazil.
LA  - eng
GR  - FIPE/HCPA - 2016-0412/Fundo de Incentivo a Pesquisa e Eventos/
GR  - CNPq - 309916/2017-8/Conselho Nacional de Desenvolvimento Cientifico e 
      Tecnologico/
PT  - Journal Article
DEP - 20200116
PL  - United States
TA  - Int J Dev Neurosci
JT  - International journal of developmental neuroscience : the official journal of the 
      International Society for Developmental Neuroscience
JID - 8401784
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neural Cell Adhesion Molecules)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (platelet-derived growth factor A)
RN  - EC 1.3.8.6 (Glutaryl-CoA Dehydrogenase)
RN  - EC 3.4.23.5 (Cathepsin D)
RN  - Glutaric Acidemia I
SB  - IM
MH  - Amino Acid Metabolism, Inborn Errors/*blood/complications
MH  - Biomarkers/blood
MH  - Brain Diseases, Metabolic/*blood/complications
MH  - Brain-Derived Neurotrophic Factor/*blood
MH  - Cathepsin D/*blood
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Glutaryl-CoA Dehydrogenase/blood/*deficiency
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Nerve Degeneration/blood/*diagnosis/etiology
MH  - Neural Cell Adhesion Molecules/blood
MH  - Platelet-Derived Growth Factor/metabolism
OTO - NOTNLM
OT  - brain-derived neurotrophic factor
OT  - glutaric aciduria type I
OT  - neurodegeneration
EDAT- 2020/01/08 06:00
MHDA- 2020/11/20 06:00
CRDT- 2020/01/08 06:00
PHST- 2019/12/11 00:00 [received]
PHST- 2019/12/13 00:00 [accepted]
PHST- 2020/01/08 06:00 [pubmed]
PHST- 2020/11/20 06:00 [medline]
PHST- 2020/01/08 06:00 [entrez]
AID - 10.1002/jdn.10006 [doi]
PST - ppublish
SO  - Int J Dev Neurosci. 2020 Feb;80(1):42-49. doi: 10.1002/jdn.10006. Epub 2020 Jan 
      16.