An unusual cause of “pink diaper” in an infant: Answers

The possible etiologies of crystalluria in an infant include hypercalciuria, distal renal tubular acidosis (d-RTA), primary hyperoxaluria, cystinuria, hyperuricosuria and—rarely—increased excretion of other purine and pyrimidine metabolites, such as 2,8-dihydroxyadenine, xanthine, hypoxanthine, and orotic acid [1]. Our patient did not have evidence of metabolic acidosis, hypercalciuria, hypocitraturia, hyperoxaluria, or aminoaciduria, thereby ruling out crystalluria secondary to disorders causing hypercalciuria, d-RTA, primary hyperoxaluria, and cystinuria. We therefore focused further investigation on disorders of purine metabolism which can present with altered uric acid levels in plasma and urine [2]. Hyperuricosuria may be physiological due to increased excretion of uric acid in neonates. Hyperuricosuria in combination with hyperuricemia may be associated with hypoxanthine–guanine phosphoribosyl transferase (HPGRT) deficiency and glycogen storage disorders. Hypouricosuria can be seen in xanthine dehydrogenase (XDH) deficiency which is associated with increased excretion of xanthine and hypoxanthine. Adenine phosphoribosyl transferase (APRT) deficiency leads to increased urinary 2,8-dihydroxyadenine (2,8-DHA), with uric acid excretion being normal [3].

Further testing should include:

In our patient, increased urinary excretion of xanthine and hypoxanthine and low FeUA along with severe hypouricemia, normal APRT enzyme activity, and normal SO level were diagnostic of hereditary xanthinuria.

Hypouricemia can be associated with several conditions that can be further classified based on FeUA. Low FeUA is seen in hereditary xanthinuria and is also associated with the use of allopurinol or rasburicase, as well as low dietary purine intake. Hypouricemia with normal-to-high FeUA is seen in hereditary renal hypouricemia, syndrome of inappropriate antidiuretic hormone, and conditions causing generalized proximal tubulopathy, such as Wilson’s disease, Fanconi syndrome, and cystinosis [4]. Hypouricemia to the degree of severity seen in our patient is rarely seen in conditions other than xanthinuria or hereditary renal hypouricemia, while patients with APRT deficiency have mild hypouricemia.