Adenine Phosphoribosyltransferase Deficiency

Abstract

SummaryComplete adenine phosphoribosyltransferase (APRT) deficiency is a rare inherited metabolic disorder that leads to the formation and hyperexcretion of 2,8-dihydroxyadenine (DHA) into urine. The low solubility of DHA results in precipitation of this compound and the formation of urinary crystals and stones. The disease can present as recurrent urolithiasis or nephropathy secondary to crystal precipitation into renal parenchyma (DHA nephropathy). The diagnostic tools available-including stone analysis, crystalluria, and APRT activity measurement-make the diagnosis easy to confirm when APRT deficiency is suspected. However, the disease can present at any age, and the variability of symptoms can present a diagnostic challenge to many physicians. The early recognition and treatment of APRT deficiency are of crucial importance for preventing irreversible loss of renal function, which still occurs in a nonnegligible proportion of cases. This review summarizes the genetic and metabolic mechanisms underlying stone formation and renal disease, along with the diagnosis and management of APRT deficiency.

The Purine Salvage Pathway and the Restoration of Cerebral ATP: Implications for Brain Slice Physiology and Brain Injury

“…High doses of adenine, however, result in toxicity and pathology associated with the xanthine oxidase-mediated conversion of adenine to the insoluble 2,8 dihydroxyadenine, which forms crystals, primarily in the kidney. This occurs in APRT deficiency, but can be managed via the use of the xanthine oxidase inhibitor, allopurinol [108]. Given this concern, the introduction of adenine as a component of blood transfusion products was delayed in some countries until extensive animal and human studies established safe limits for intravenous infusion, which are in the region of 10-15 mg/kg [109].…”

Adenine Phosphoribosyltransferase Deficiency as a Rare Cause of Renal Allograft Dysfunction

“…Infrared spectroscopy allows correct identification. 3,4 By light microscopy, crystals may resemble calcium oxalate; however, they appear brown on the hematoxylin and eosin stain, whereas calcium oxalate crystals are optically clear. 4,6 DHA crystals reflect light in polarized or phase-contrast microscopy (Figures 2 and 3).…”

“…Crystals may lack the typical features of DHA. 3,4 Clinical presentation can be AKI, CKD, or acute allograft dysfunction in patients with no previous stone history. 4 Most cases have been reported from Iceland, Japan, and France.…”

“…1 DHA is protein-bound in plasma but extremely insoluble in urine, leading to the formation of crystals and subsequently, stones or precipitation in renal parenchyma, which causes crystalline nephropathy. 2,3 Both these conditions can occur together or separately. 3 The kidneys and urinary tract system seem to be the only organs affected by APRT deficiency.…”

“…2,3 Both these conditions can occur together or separately. 3 The kidneys and urinary tract system seem to be the only organs affected by APRT deficiency. 4 Prevalence of APRT deficiency is largely unknown, and some mutations have high frequency in certain countries.…”