Abstract: Background – In the process of heme degradation, biliverdin reductase catalyzes the conversion of biliverdin to bilirubin. While rare defects in the biliverdin reductase A gene (BLVRA) cause biliverdinuria in human patients, this disorder has not yet been reported in dogs. Hypothesis/Objectives – The objective was to identify biliverdinuria and the pathogenic BLVRA variant in a dog with green urine. Animals – A three-year-old mixed breed dog with green urine compared to control dogs, including a database of whole genome sequencing variants. Methods – Beside routine clinicopathological evaluations, urinary mass spectroscopy and whole genome sequencing studies focusing on BLVRA were performed. Results – The mixed breed dog exhibited persistently green urine since juvenile age. The dog also had a chronic regenerative anemia which remained unexplained. Urine metabolic screening of bilirubin pathway metabolites revealed increased biliverdin concentrations. Whole genome sequencing revealed a 19 kb homozygous deletion in the BLVRA gene that spanned the final three of seven exons (ENSCAFT00805017018.1, p.Gly118-*297del) predicting a major truncation or premature mRNA decay. None of 671 dogs from 63 breeds in the genomic database were homozygous for the BLVRA deletion. Conclusions and clinical importance – This study documents biliverdinuria due to a major BLVRA deletion as the cause of persistent green urine in a dog. To the authors’ knowledge, this is the first confirmed case of biliverdinuria in a dog and illustrates the use of targeted metabolic and genomic screening as key diagnostic tools. Genotyping for the BLVRA deletion may help identify other affected dogs.
