Abstract
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 spectrum and 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.