Rapid method for the diagnosis of partial adenine phosphoribosyltransferase deficiencies causing 2,8-dihydroxyadenine urolithiasis

Abstract

More than half of the Japanese patients with 2,8-dihydroxyadenine urolithiasis only partially lack adenine phosphoribosyltransferase (APRT), while all the Caucasian patients with the same disease completely lack the enzyme. APRT activities in healthy heterozygotes for the complete APRT deficiencies were at the same levels as the Japanese patients, and simple enzyme assay does not distinguish between these two conditions. We have previously shown, using viable T-cells, that the enzyme was non-functional in the cells from the Japanese patients although they contain considerable APRT activities in the cell extracts. In the present investigations, we devised a rapid method using erythrocytes for the diagnosis of partial APRT deficiencies accompanied by severe impairment in adenine metabolism causing 2,8-dihydroxyadenine lithiasis. Thus, erythrocytes from three different families with 2,8-dihydroxyadenine urolithiasis associated with partial APRT deficiencies incorporated only minimal amounts of radioactive adenine, while normal erythrocytes incorporated significant amounts. These data indicate that severe impairment in adenine metabolism is shown not only in viable T-cells but also in viable erythrocytes. The present procedures provide a rapid method suitable for routine clinical use for the diagnosis of partial APRT deficiencies causing 2,8-dihydroxyadenine lithiasis.

Estudos estruturais e correlação com a síndrome urolitíase de mutantes da adenina fosforribosiltransferase humana

“…Já o tipo II da doença caracteriza-se por apresentar significante atividade da APRT em lisados celulares, entre 10 a 25% da enzima normal em hemolisados, e aparenta ser exclusivo da população japonesa [65][66][67][68][69][70][71][72][73] . O alelo mutante que codifica esse tipo da doença é denominado APRT*J e caracterizado pela mutação M136T, sendo seus pacientes também homozigotos para o alelo M136T ou compõem heterozigose para M136T/alelo inativo.…”