Adenine Phosphoribosyltransferase Deficiency: A Potentially Reversible Cause of CKD

An Unusual Course of a 2,8-Dihydroxyadeninuria Crystalline Nephropathy Secondary to Adenine Phosphoribosyltransferase Deficiency

“…The variant found in our patient, p (Gly63Asp), has previously been described as disease causing for APRT deficiency by Bollee et al [11] in 2010, Kaartinen et al [12] in 2014, and Li et al [2] in 2019, with a total of 4 cases of this specific mutation, 3 of them being from Lebanese descent and the fourth from middle eastern origins. If we review the phenotype of the cases described, we find differences in terms of presentation and evolution.…”

“…The disorder is characterized by urinary excretion of 2,8-DHA which is poorly soluble, leading to crystal aggregation and deposition within the tubular lumen, causing obstruction. Another end point is their deposition and uptake in the epithelial cells, causing tubular injury, an inflammatory environment with rupture of the tubules, and deposition into the interstitium leading to interstitial fibrosis and tubular atrophy [2]. The disorder is characterized by urolithiasis and chronic kidney disease sometimes leading to end-stage disease, or as a recurrence after the kidney transplant with a frequent loss of renal allograft [3].…”

Recurrence of 2,8-dihydroxyadenine Crystalline Nephropathy in a Kidney Transplant Recipient: A Case Report and Literature Review

“…Measurement of the APRT activity in red cell lysates or the performance of molecular genetic testing is suggested to confirm the diagnosis of this disorder. (20,22) A stone analysis and the APRT activity in red cell lysates were not performed in our patient. Instead, genetic testing was performed, showing a pathogenic homozygous variant.…”

“…2,8-DHA is protein-bound in plasma but poorly soluble in the urine at any physiological pH and forms crystals in tubular lumens, tubular epithelial cells, and the interstitium, resulting in inflammation, necrosis, and fibrosis (15,(21)(22)(23). Notably, inflammation is characterized by mononuclear cell infiltrates (23), and 2,8-DHA crystals are surrounded by giant cells as well as macrophages on renal biopsies (4,15,17,22). Inflammation and necrosis accompanied by crystal deposition may be confused with rejection in transplant patients.…”

“…In most crystalluria specimens, 2,8-DHA crystals are round and reddish-brown when viewed by urine microscopy and show a typical central Maltese cross pattern on polarized light microscopy. In the clinical field, Fourier transform infrared microscopy has been accepted as an accurate method for identifying 2,8-DHA crystals (20,22,24). However, a diagnosis of APRT deficiency based on the analysis of 2,8-DHA crystals and urolithiasis is not sufficient.…”