NMR spectroscopic studies on the late onset form of 3-methylglutaconic aciduria type I and other defects in leucine metabolism

Autor: Ronald J.A. Wanders, Berry Kremer, Ference J. Loupatty, Udo F. H. Engelke, Marinette van der Graaf, Erik van den Bergh, Eva Morava, Leo A. J. Kluijtmans, Sandra Loss, Detlef Moskau, Ron A. Wevers
Rok vydání: 2006
Předmět:
medicine.medical_specialty
Magnetic Resonance Spectroscopy
Energy and redox metabolism [NCMLS 4]
Urine
Neuroinformatics [DCN 3]
Meglutol
Genomic disorders and inherited multi-system disorders [IGMD 3]
Glutarates
Leukoencephalopathy
White matter
Cerebrospinal fluid
Leucine
In vivo
Internal medicine
Perception and Action [DCN 1]
Valerates
medicine
Humans
Radiology
Nuclear Medicine and imaging
Amino Acid Metabolism
Inborn Errors
Spectroscopy
Chemistry
Brain
Nuclear magnetic resonance spectroscopy
Glycostation disorders [IGMD 4]
Middle Aged
3-Methylglutaconic Aciduria
medicine.disease
Neuromuscular development and genetic disorders [UMCN 3.1]
Mitochondrial medicine [IGMD 8]
Endocrinology
medicine.anatomical_structure
Genetic defects of metabolism [UMCN 5.1]
Molecular Medicine
Female
Functional Imaging [UMCN 1.1]
Zdroj: NMR in Biomedicine, 19, 2, pp. 271-8
NMR in Biomedicine, 19, 271-8
ISSN: 1099-1492
0952-3480
DOI: 10.1002/nbm.1018
Popis: Contains fulltext : 50036.pdf (Publisher’s version ) (Closed access) A diagnosis of 3-methylglutaconic aciduria type I (OMIM: 250950) based on elevated urinary excretion of 3-methylglutaconic acid (3MGA), 3-methylglutaric acid (3MG) and 3-hydroxyisovaleric acid (3HIVA) was made in a 61-year-old female patient presenting with leukoencephalopathy slowly progressing over more than 30 years. The diagnosis was confirmed at the enzymatic and molecular level. In vivo brain MR spectroscopic imaging (MRSI) was performed at 3.0 T, and one-dimensional and two-dimensional in vitro NMR spectroscopy of body fluids of the patient was performed at 11.7 T. Additionally, we measured 1D (1)H-NMR spectra of urine of seven patients with a total of four different inborn errors of leucine metabolism. Increased concentrations of 3HIVA, 3MGA (cis and trans) and 3MG were observed in the NMR spectra of the patient's urine. In the cerebrospinal fluid, the 3HIVA concentration was 10 times higher than in the plasma of the patient and only the cis isomer of 3MGA was observed. In vivo brain MRSI showed an abnormal resonance at 1.28 ppm that may be caused by 3HIVA. Comparison of (1)H-NMR spectra of urine samples from all eight patients studied, representing five different inborn errors of leucine metabolism, showed that each disease has typical NMR characteristics. Our leukoencephalopathy patient suffers from a late-onset form of 3-methylglutaconic aciduria type I. In the literature, only very few adult patients with this conditions have been described, and 3HIVA accumulation in white matter in the brain has not been presented before in these patients. Our data demonstrate that (1)H-NMR spectroscopy of urine can easily discriminate between the known inborn errors of leucine metabolism and provide the correct diagnosis.
Databáze: OpenAIRE
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