A case of 2,8-DHA crystalline nephropathy caused by adenine phosphoribosyltransferase deficiency: diagnosis and treatment

Abstract

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder that leads to the accumulation of poorly soluble 2,8-dihydroxyadenine (DHA) in the kidneys, resulting in a variety of renal presentations including nephrolithiasis, acute kidney injury, and chronic kidney disease (CKD) caused by crystal nephropathy. Here, we report a case of a 43-year-old man with 2,8-DHA crystalline nephropathy caused by APRT deficiency strongly suspected by renal biopsy results and definitively diagnosed by a urine gas chromatography-mass spectrometry (GC/MS)-based plasma metabolomic assessment. This case represents the importance of awareness and recognition of the signs and symptoms of this rare condition and its progression to CKD, which can be prevented by the early administration of xanthine oxidoreductase inhibitors.

Keywords: 2,8-Dihydroxyadenine crystal nephropathy; Adenine phosphoribosyltransferase deficiency; Xanthine oxidoreductase.

Fig. 1

Computed tomography image. The kidney stone is indicated by the arrow

Fig. 2

Masson-trichrome staining showing a high degree of interstitial fibrosis within the renal capsule (scale bar, 50 μm)

Fig. 3

Periodic acid-methenamine-silver staining showing green/brown crystalline material within the tubular lumina and epithelial cells, eliciting a multinucleate giant cell reaction (arrows) (scale bar, 50 μm)

Fig. 4

Polarized light microscopy showing the clearly refractile crystals (scale bar, 50 μm)

Fig. 5

Results of the urine metabolome by GC/MS. The retention time of 8-hydroxyadenine, 2, 8-DHA, and adenine are indicated by an arrow

Fig. 6

Clinical course. Cre creatinine, UA uric acid