Adenine phosphoribosyltransferase syndrome

A J Pawlak, J S Zaremba, J Barankiewicz, E Zdzienicka, and B Czartoryska, Effect of blood transfusion on activities of hypoxanthine-guanine phosphoribosyltransferase and adenine phosphoribosyltransferase in circulating red blood cells of a patient with Lesch-Nyhan syndrome, Acta Med Pol 19 331 (1978) ... 

Increased intracellular levels of PP-ribose-P have been implicated in the cause of certain hyperuricemic states associated with uric acid overproduction. Fibroblasts from two patients with the Lesch-Nyhan syndrome were found previously to have an elevated intracellular concentration of PP-ribose-P with a normal rate of PP-ribose-P production (Rosenbloom, et al., 1968). Green and Seegmiller (1969) subsequently reported a mean PP-ribose-P value of 47.1 in erythrocytes from seven patients with HGPRT deficiency. We have confirmed these elevated PP-ribose-P levels in three additional patients with the Lesch-Nyhan syndrome with values of 20.5, 39.4 and 49.5 juM (Table 1). The mothers of these patients are obligate heterozygotes and have normal PP-ribose-P levels. Two diseases associated with a deficiency of other PRT enzymes are not associated with altered erythrocyte PP-ribose-P levels (Table 1). PP-ribose-P levels were in the normal range in one patient with a partial deficiency of adenine phosphoribosyltransferase (APRT) and in one patient with orotic aciduria, which is due to a deficiency... 

Adenine and one of its analogs, 2,6-diaminopurine, react with PP-ribose-P in the presence of adenine phosphoribosyltransferase (APRT) to form their respective ribonucleotide derivatives. Both of these compounds were reported by Schulman, et al. (1971) to cause a substantial drop in erythrocyte PP-ribose-P levels when administered to a patient with the Lesch-Nyhan syndrome. In 1 gouty patient given adenine 1 gram, a maximum decrease in erythrocyte PP-ribose-P levels to 25% of control values occurred within three hours (Fig. 3). Adenine has also been shown to be an inhibitor of purine synthesis de novo in normal and gouty subjects (Seegmiller, et al., 1968). 

The Lesch-Nyhan Syndrome (LNS) is a rare x-linked neurological disease of children characterized by choreoathetosis, spasticity, mental retardation and compulsive self mutilation accompanied by excessive purine production and hyperuricemia (l). The virtually complete deficiency of activity of a purine salvage enzyme, hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) (EC 2.4.2.8.) (2), due to structural gene mutation (3 4) has been shown to be the basic abnormality in this disease. In erythrocytes of LNS patients, HGPRT deficiency has been found to be associated with increased activity and relative thermal stability of adenine phosphoribosyltransferase (APRT) (EC 2.4.2.7 ) (5 6) an autosomally determined enzyme (7) ... 

Recent advances in the understanding of human purine metabolism have been stimulated by the discovery of specific inborn errors of this pathway in man. In particular, the demonstration of the deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) in the Lesch-Nyhan syndrome and in some patients with gout has contributed essential information on the regulation of purine biosynthesis novo and on the critical role of this reutilization pathway in central nervous system function in man. The search for other disorders led to the description of a partial deficiency of adenine phosphoribosyltransferase (APRT) in four members in three generations of one family. Each of the subjects partially deficient in APRT exhibited a normal serum urate concentration and the propositus had a normal excretion of uric acid (Kelley, et al., 1968). We have investigated a second family partially deficient in APRT (Fox and Kelley, in press). 

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