Naslov
Sensitivity and specificity of free and total glutaric acid and 3-hydroxyglutaric acid measurments by stable-isotope dilution assays for the diagnosis of glutaric aciduria type I

Autori
Batrić, Ivo ; Wagner, L. ; Feyh, P. ; Liesert, M. ; Buckel, W. ; Hoffman, G. F.

Izvornik
Journal of Inherited Metabolic Disease (0141-8955) 22 (1999), 8; 867-882

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
glutaric aciduria; child

Sažetak
Glutaric aciduria type I (GA I) is a recessive disorder caused by a deficiency of glutaryl-CoA dehydrogenase (GCDH). The biochemical hallmark of the disease is the accumulation of glutaric acid and, to a lesser degree, of 3-hydroxyglutaric acid and glutaconic acid in body fluids and tissues. A substantial number of patients show only slightly, intermittently elevated or even normal urinary excretion of glutaric acid, which makes early diagnosis and treatment to prevent the severe neurological sequelae ditficult. Furthermore, elevated urinary excretion of glutaric acid can also be found in a number of other disease states, mostly related to mitochondrial dysfunction. Stable-isotope dilution assays were designed for both glutaric acid and 3hydroxyglutaric acid and their diagnostic sensitivity and specificity were evaluated. Control ranges of glutaric acid in urine were 1.1-9.7 mmol/mol creatinine before and 4.1-32 after hydrolysis. The respective values of 3-hydroxyglutaric acid were 1.4-8.0 and 2.6-11.7 mmol/mol creatinine. For other body fluids, control ranges in lcmol/L were: for glutaric acid 0.55-2.9 (plasma), 0.18-0.63 (cerebrospinal fluid) and 0.19-0.7 (amniotic fluid) ; and for 3-hydroxyglutaric acid, 0.2-1.36 (plasma), < 02 (cerebrospinal fluid) and 022-0.41 (amniotic fluid). Twenty-five patients with GCDH deficiency were studied. Low excretors (12 patients) were defined by a urinary glutaric acid below 100 mmol/mol creatinine down into the normal range, while high excretors (13 patients) had glutaric acid excretions well above this value. With and without hydrolysis there was an overlap of glutaric acid values between patients and controls. Diagnostic sensitivity and specificity of 100% could only be achieved by the quantitative deter mination of 3-hydroxyglutaric acid with the newly developed stable-isotopedilution assay, allowing an accurate diagnosis of all patients, regardless of the amount of glutaric acid excreted in urine.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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