Correspondence LETTER TO THE EDITOR Febuxostat in Adenosine Phosphoribosyltransferase Deficiency To the Editor: Adenosine phosphoribosyltransferase (APRT) deficiency is inherited in an autosomal recessive manner. Lack of APRT activity directs the metabolism of adenine to 2,8-dihydroxyadenine, a reaction catalyzed by xanthine dehydrogenase.1 Crystallization of 2,8-dihydroxyadenine in urine and tubulointerstitial tissue leads to urolithiasis and crystalline nephropathy.2 Treatment with the xanthine dehydrogenase inhibitor allopurinol reduces the amount of crystals in the urine and halts the progression of damage if treatment is started in time.3 A 35-year-old woman had a history of radiolucent kidney stones since early childhood. The diagnosis of APRT deficiency was confirmed by a genetic analysis showing a biallelic missense mutation (substitution of the aspartate at amino acid 65 with valine). Unfortunately, she is allergic to allopurinol. In January 2010, the patient was

prescribed febuxostat, a xanthine dehydrogenase inhibitor, at the dose of 80 mg daily. At that time, her serum creatinine concentration was 1.37 mg/dL (estimated glomerular filtration rate [eGFR], 48 mL/min/1.73 m2) and, as always, the pathognomonic brown and spherical 2,8-dihydroxyadenine crystals were abundant in her urine (Fig 1). Upon treatment, the crystalluria promptly disappeared. There have been no signs of kidney stones, and the serum creatinine concentration has decreased to 1.10 mg/dL (eGFR, 60 mL/min/1.73 m2). No side effects of febuxostat have been observed. APRT deficiency is a rare disease, but studies indicate that it is gravely underdiagnosed.4 However, awareness of the disease seems to be increasing, which emphasizes the importance of the availability of safe and effective therapy. The present account is the first report to my knowledge of febuxostat treatment in APRT deficiency. Margrét Árnadóttir, MD, PhD Landspitali University Hospital Hringbraut Reykjavík, Iceland Corresponding author: [email protected]

Acknowledgements Financial Disclosure: The author declares that she has no relevant financial interests.

References 1. Simmonds HA, Van Acker KJ, Cameron JS, McBurney A. Purine excretion in complete adenine phosphoribosyltransferase deficiency: effect of diet and allopurinol therapy. Adv Exp Med Biol. 1977;76B:304-311. 2. Fye KH, Sahota A, Hancock DC, et al. Adenosine phosphoribosyltransferase deficiency with renal deposition of 2,8dihydroxyadenine leading to nephrolithiasis and chronic renal failure. Arch Intern Med. 1993;153:767-770. 3. Bollée G, Harambat J, Bensman A, Knebelmann B, Daudon M, Cebbalos-Picot I. Adenine phosphoribosyltransferase deficiency. Clin J Am Soc Nephrol. 2012;7:1521-1527. 4. Ceballos-Picot I, Perignon JL, Hamet M, Daudon M, Kamoun P. 2,8-Dihydroxyadenine urolithiasis, an underdiagnosed disease. Lancet. 1994;339:1050-1051. Figure 1. Different sizes of the typical 2,8-dihydroxyadenine crystals. The urine preparation is unstained (original magnification, 3400).

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Febuxostat in adenosine phosphoribosyltransferase deficiency.

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