Xanthinuria due to xanthine dehydrogenase (XDH) deficiency is a rare genetic disorder characterized by hypouricemia and the accumulation of xanthine in the urine. We have identified an Afghan girl whose xanthinuria could be classified as type I xanthinuria based on an allopurinol loading test. Three mutations were identified in the XDH gene, 141insG, C2729T (T910M) and C3886T (R1296W). Site-directed mutagenesis followed by expression analysis in Escherichia coli revealed that not only the frame shift mutation 141insG impairs XDH activity, but also the missense mutation C2729T, while C3886T resulted in major residual activity of about 50% of the wild type. In this report, a case of xanthinuria type I with mutations of XDH was identified and characterized by expression studies.