Accumulation of 2,8 Dihydroxyadenine in Bovine Liver, Kidneys, and Lymph Nodes

Abstract

A variety of tissues from 20 cattle slaughtered at federally inspected facilities contained abundant light green to greenish-yellow material. Gross lesions were most common in the liver and hepatic lymph nodes. Less frequent lesions were present in the mediastinal, renal, intercostal, and gastric lymph nodes. The material was most prominent in the portal triads, and in the medullary sinuses of the lymph nodes, at times occupying up to one half of the nodal mass. Renal calculi were present in one animal. Histologically, the condition was characterized by the intracytoplasmic accumulation of innumerable brown, acicular crystals in hepatocytes, macrophages, and renal tubular epithelial cells. Less frequent large aggregates of extracellular crystals were found in the lumens of renal tubules and in portal triads. Crystals were highly birefringent when examined using polarized light. The crystals were identified as 2,8 dihydroxyadenine using X-ray diffraction, electron diffraction, infrared spectroscopy, and mass spectrometry. In mammals, adenine is normally converted to adenylate by the enzyme adenine phosphoribosyltransferase. When adenine phosphoribosyltransferase is absent, deficient, or inhibited, adenine is oxidized to 2,8 dihydroxyadenine, which is extremely insoluble at physiological pH. In human beings, an autosomal recessive disease known as 2,8 dihydroxyadeninuria is caused by a deficiency of adenine phosphoribosyltransferase.