Silent increase of urinary ethylmalonic acid is an indicator of nonspecific brain dysfunction.
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.
Zannolli
Raffaella
R
Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Siena, Italy. zannolli@unisi.it
Buoni
Sabrina
S
Tassini
Maria
M
De Nicola
Anna
A
Betti
Gianni
G
De Felice
Claudio
C
Orsi
Alessandra
A
Varetti
Maria Concetta
MC
Ferrara
Francesco
F
Messina
Mario
M
Giannini
Cosimo
C
Mohn
Angelika
A
Chiarelli
Francesco
F
Liberati
Marco
M
Strambi
Mirella
M
Funghini
Silvia
S
Vivi
Antonio
A
Wevers
Ron A
RA
Hayek
Joseph
J
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
D015415:Biomarkers; D008314:Malonates; C038080:ethylmalonic acid