Diagnosis Of Adenine Phosphoribosyltransferase Deficiency Research Articles

Are conventional stone analysis techniques reliable for the identification of 2,8-dihydroxyadenine kidney stones? A case series.

We have recently encountered patients incorrectly diagnosed with adenine phosphoribosyltransferase (APRT) deficiency due to misidentification of kidney stones as 2,8-dihydroxyadenine (DHA) stones. The objective of this study was to examine the accuracy of stone analysis for identification of DHA. Medical records of patients referred to the APRT Deficiency Research Program of the Rare Kidney Stone Consortium in 2010-2018 with a diagnosis of APRT deficiency based on kidney stone analysis were reviewed. The diagnosis was verified by measurement of APRT enzyme activity or genetic testing. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectra of pure crystalline DHA and a kidney stone obtained from one of the confirmed APRT deficiency cases were generated. The ATR-FTIR spectrum of the kidney stone matched the crystalline DHA spectrumand was used for comparison with available infrared spectra of stone samples from the patients. Of 17 patients referred, 14 had sufficient data available to be included in the study. In all 14 cases, the stone analysis had been performed by FTIR spectroscopy. The diagnosis of APRT deficiency was confirmed in seven cases and rejected in the remaining seven cases. Comparison of the ATR-FTIR spectrum of the DHA stone with the FTIR spectra from three patients who did not have APRT deficiency showed no indication of DHA as a stone component. Misidentification of DHA as a kidney stone component by clinical laboratories appears common among patients referred to our program. Since current clinical protocols used to interpret infrared spectra for stone analysis cannot be considered reliable for the identification of DHA stones, the diagnosis of APRT deficiency must be confirmed by other methods.

Diagnosis of adenine phosphoribosyltransferase deficiency as the underlying cause of renal failure in a renal transplant recipient

Adenine phosphoribosyltransferase (APRT) deficiencyis a rare inborn error of metabolism first described inthe UK in 1976 [1]. It is inherited as an autosomalrecessive trait and the gene is located on chromosome16. APRT is a salvage enzyme that normally catalysesthe conversion of adenine to adenine monophosphateusing PP-ribose-P. Deficiency results in adenine accu-mulation with conversion to and excretion of 2,8-dihydroxyadenine (2,8-DHA) in the urine. 2,8-DHA isprotein-bound in plasma, but is extremely insoluble inurine at any pH. Tubular crystal deposition can occurassociated with marked interstitial fibrosis and/orurolithiasis. Since its original description, APRTdeficiency has been recognized increasingly as a causeof chronic renal failure. We report a case of APRTdeficiency that was diagnosed after renal transplanta-tion. This has led to specific treatment for the patienttoreducetheriskoffurthercrystalandstoneformationin the transplanted kidney. Also, additional familymembers with the condition have been identifiedthrough family screening.