Anderson Büker de Oliveira

Selective screening for organic acidemias by urine organic acid GC–MS analysis in Brazil: Fifteen-year experience

BACKGROUND The gas chromatography/mass spectrometry (GC/MS) method for organic acid analysis was established in developed countries since 1980s, but due to the small number of experienced clinical biochemists in this field and also the short availability of mass spectrometers scarce reports exist on the prevalence of organic acidemias (OAs) in developing countries like Brazil. METHODS During January 1994 to July 2008, we analyzed organic acids by GC/MS in urine specimens obtained from Brazilian children with clinical suspicion of metabolic diseases. RESULTS Two hundred and thirty four cases of disorders of organic acid metabolism, including 218 OAs (3.17%), were diagnosed among 6866 patients investigated. The most frequent disorders were primary lactic acidemia (57), methylmalonic acidemia (34), glutaric acidemia type I (33), propionic acidemia (18), 3-hydroxy-3-methylglutaric aciduria (17), L-2-hydroxyglutaric aciduria (9) and multiple carboxylase deficiency (9). Fourteen cases of mitochondrial fatty acid oxidation disorders, as well as 12 aminoacidopathies and 4 cases of vitamin B12 deficiency were also detected. Prompt treatment following diagnosis led to a better outcome in a considerable number of patients. CONCLUSION Detection of OAs in loco in developing countries is important despite the implied extra costs, since it allows rapid therapy in many cases with a significant reduction of morbidity and mortality and makes the physicians more aware of these pathologies.

Neurochemical evidence that pristanic acid impairs energy production and inhibits synaptic Na(+), K(+)-ATPase activity in brain of young rats.

Pristanic acid (Prist) accumulates in some peroxisomal disorders characterized by neurologic dysfunction and brain abnormalities. The present work investigated the in vitro effects of Prist on important parameters of energy metabolism in brain cortex of young rats. CO2 production from labeled acetate and the activities of the respiratory chain complexes I–IV, creatine kinase and synaptic Na+, K+-ATPase were measured. Prist decreased CO2 production and the activities of complexes I, II and II–III. Prist also reduced Na+, K+-ATPase activity, but did not affect the activity of creatine kinase. Considering the importance of the citric acid cycle and the electron flow through the respiratory chain for brain energy production and of Na+, K+-ATPase for the maintenance of membrane potential, the present data indicate that Prist compromises brain bioenergetics and neurotransmission. It is presumed that these pathomechanisms may be involved in the neurological damage found in patients affected by disorders in which Prist accumulates.