Adenine phosphoribosyltransferase deficiency

H5. Hidaka, Y., Tarle, S. A., Fujimori, S Kamatani, N Kelley, W. N., and Palella, T. D., Human adenine phosphoribosyltransferase deficiency Demonstration of a single mutant allele common to the Japanese. J. Clin. Invest. 81,945-950 (1988). 

K2. Kamatani, N., Hakoda, M., Otsuka, S., Yoshikawa, H., and Kashiwazaki, S., Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients. J. Clin. Invest. 90, 130-135 (1992). 

Problems of Diagnosis and Treatment in a New Defect-Adenine Phosphoribosyltransferase Deficiency... 

Complete Adenine Phosphoribosyltransferase Deficiency with 2,8-Dihydroxyadenine Stone Formation... 

W.N. Kelley, R.I. Levy, F.M. Rosenbloom, J.F. Henderson, and J.E. Seegmiller, Adenine phosphoribosyltransferase deficiency a previously undescribed genetic defect in man, Clin. Invest. 47 2281-2289 (1968). 

Further genes involved in other conditions responsible for renal stone development among many others could be identified e.g. osteopetrosis with tubular acidosis type 1 (xanthinoxidase), hyperoxaluria typel (alanine-glyoxylate-aminotrans-ferase), adenine-phosphoribosyltransferase deficiency (ATRTase), distal tubular acidosis and primary hypomagnesemia. 

ADENINE PHOSPHORIBOSYLTRANSFERASE DEFICIENCY REPORT OF A SECOND FAMILY... 

Fig. 4. Effect of administration of oral adenine on erythrocyte PRPP levels in adenine phosphoribosyltransferase deficiency.

ADENINE PHOSPHORIBOSYLTRANSFERASE DEFICIENCY IN A FEMALE WITH GOUT... 

Further evaluation of adenine phosphoribosyltransferase deficiency in man. Occurrence in a patient with gout. Clin. Res. 18, 53. 

Adenine phosphoribosyltransferase (APRT) deficiency is an inherited disorder of purine metabolism and is inherited in an autosomal recessive manner (K18, V7). This enzyme deficiency results in an inability to salvage the purine base adenine, which is oxidized via the 8-hydroxy intermediate by xanthine oxidase to 2,8-di-hydroxyadenine (2,8-DHA). This produces crystalluria and the possible formation of kidney stones due to the excretion of excessive amounts of this insoluble purine. Type I, with virtually undetectable enzyme activity, found predominantly in Caucasians, is found in homozygotes or compound heterozygotes for null alleles. Type II, with significant APRT activity, found only in Japan, is related to a missense mu-... 

Barratt, T.M., Simmonds, H.A. Cameron, J.S., Potter, C.F. Rose, G.A., Arkell, D.G., Williams, D.I. Complete deficiency of adenine phosphoribosyltransferase, a third case presenting as renal stones in a young child. Arch. Dis. Child, 54 25, 1979. 

Kuroda, M., Miki T., Kiyohara, H., Usami, M., Nakamura, T., Kotake, T., Takemoto, M., Sonoda, T- Urolithiasis composed of 2,8-dihydroxyadenine due to partial deficiency of adenine phosphoribosyltransferase. Report of a case (author s transl.) Nippon Hinyokika Gakkal Azsshi 1980 71(3) 283-8. 

In 1968 Kelley (1) described for the first time a patient with a partial adenine phosphoribosyltransferase (APRT) deficiency. Since that time many families have been found with this abnormality in,the heterozygous state. Though in some families gout could be detected, no consistent correlation with gout or hyperuricemia was noted. No clinical disorder has yet been found to be consistently associated with a partial deficiency of APRT. The incidence in the population has been estimated to be 0.5 to 1% (2). 

GENETIC MECHANISM(S) RESPONSIBLE FOR A DEFICIENCY OF ADENINE PHOSPHORIBOSYLTRANSFERASE IN MAN... 

Adenine phosphoribosyltransferase (APRT) is a relatively non-abundant soluble enzyme which in man is coded for by a single structural gene on chromosome 16 (1). A partial deficiency of APRT in man was first described in 1968 (2). These subjects were asymptomatic and were shown to be heterozygous for the enzyme defect. 

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... 

---