title: Silent increase of urinary ethylmalonic acid is an indicator of nonspecific brain dysfunction.
abstract: Our aim was to compare urinary ethylmalonic acid (EMA) levels in subjects who had no apparent clinical reason to have increased levels of this substance but were suffering from non-specific CNS impairment, and healthy controls. Urinary EMA concentrations detected by (1)H-NMR spectroscopy were studied in 130 subjects with CNS impairment of unknown origin (with no definite diagnosis, no specific symptoms or signs, and normal common biochemical and metabolic screening results) and 130 age- and sex-matched healthy subjects. EMA levels exceeding two standard deviations (SD) above normal (i.e. 8.1 mmol/molCn) were found in a subgroup of CNS-impaired patients and healthy controls. EMA levels exceeding 2 SD above normal were fourfold prevalent in the urine of patients with non-specific CNS impairment compared to from the EMA levels in healthy controls. Moreover, we found that the level exceeding > 8.1 mmol/molCn (i.e. > + 2 SD) had sufficient discrimination accuracy in identifying subjects with non-specific CNS impairment; the level exceeding 12 mmol/molCn (i.e. > + 6 SD) reaches suitable accuracy (i.e. 100% specificity and 78.6% sensitivity). These observations are of importance, as we found that subtle increases in urinary EMA levels are frequent in patients with non-specific CNS impairment. The reasons for this association remain unknown.
authors.affiliation: Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Siena, Italy. zannolli@unisi.it
authors.forename: Raffaella
authors.initials: R
authors.lastname: Zannolli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Buoni
authors.forename: Maria
authors.initials: M
authors.lastname: Tassini
authors.forename: Anna
authors.initials: A
authors.lastname: De Nicola
authors.forename: Gianni
authors.initials: G
authors.lastname: Betti
authors.forename: Claudio
authors.initials: C
authors.lastname: De Felice
authors.forename: Alessandra
authors.initials: A
authors.lastname: Orsi
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Varetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferrara
authors.forename: Mario
authors.initials: M
authors.lastname: Messina
authors.forename: Cosimo
authors.initials: C
authors.lastname: Giannini
authors.forename: Angelika
authors.initials: A
authors.lastname: Mohn
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiarelli
authors.forename: Marco
authors.initials: M
authors.lastname: Liberati
authors.forename: Mirella
authors.initials: M
authors.lastname: Strambi
authors.forename: Silvia
authors.initials: S
authors.lastname: Funghini
authors.forename: Antonio
authors.initials: A
authors.lastname: Vivi
authors.forename: Ron A
authors.initials: RA
authors.lastname: Wevers
authors.forename: Joseph
authors.initials: J
authors.lastname: Hayek
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine*; D001921:Brain / Q000503:physiopathology*; D002493:Central Nervous System Diseases / Q000503:physiopathology / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008314:Malonates / Q000652:urine*; D019906:Nuclear Magnetic Resonance, Biomolecular; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008314:Malonates; C038080:ethylmalonic acid