BACKGROUND: Uric acid is the metabolic end product of purine metabolism in humans. Altered serum and urine uric acid level (both above and below the reference ranges) is an indispensable marker in detecting rare inborn errors of metabolism. We describe different case scenarios of 4 Sri Lankan patients related to abnormal uric acid levels in blood and urine. CASE 1: A one-and-half-year-old boy was investigated for haematuria and a calculus in the bladder. Xanthine crystals were seen in microscopic examination of urine sediment. Low uric acid concentrations in serum and low urinary fractional excretion of uric acid associated with high urinary excretion of xanthine and hypoxanthine were compatible with xanthine oxidase deficiency. CASE 2: An 8-month-old boy presented with intractable seizures, feeding difficulties, screaming episodes, microcephaly, facial dysmorphism and severe neuro developmental delay. Low uric acid level in serum, low fractional excretion of uric acid and radiological findings were consistent with possible molybdenum cofactor deficiency. Diagnosis was confirmed by elevated levels of xanthine, hypoxanthine and sulfocysteine levels in urine. CASE 3: A 3-year-10-month-old boy presented with global developmental delay, failure to thrive, dystonia and self-destructive behaviour. High uric acid levels in serum, increased fractional excretion of uric acid and absent hypoxanthine-guanine phosphoribosyltransferase enzyme level confirmed the diagnosis of Lesch-Nyhan syndrome. CASE 4: A 9-year-old boy was investigated for lower abdominal pain, gross haematuria and right renal calculus. Low uric acid level in serum and increased fractional excretion of uric acid pointed towards hereditary renal hypouricaemia which was confirmed by genetic studies. CONCLUSION: Abnormal uric acid level in blood and urine is a valuable tool in screening for clinical conditions related to derangement of the nucleic acid metabolic pathway.

Department of Chemical Pathology Lady Ridgeway Hospital for Children Dr Danister De Silva Mawatha Colombo 8 Sri Lanka

Institute of Rheumatology Prague Czech Republic and Institute of Inherited Metabolic Disorders 1st Faculty of Medicine Charles University Prague Czech Republic

Nephrology Unit Lady Ridgeway Hospital for Children Colombo Sri Lanka

Neurology Unit Lady Ridgeway Hospital for Children Colombo Sri Lanka

Purine Research Laboratory St Thomas' Hospital London UK

See more in PubMed

Mraz M, Hurba O, Bartl J, Dolezel Z, Marinaki A, Fairbanks L, Stiburkova B. Modern diagnostic approach to hereditary xanthinuria. Urolithiasis. 2015;43(1):61–67. doi: 10.1007/s00240-014-0734-4. PubMed DOI

Stiburkova B, Sebesta I, Ichida K, Nakamura M, Hulkova H, Krylov V, et al. Novel allelic variant and evidence for a prevalent mutation in URAT1 causing renal hypouricemia: biochemical, genetics and functional analysis. Eur J Hum Genet. 2013;21(10):1067–1073. doi: 10.1038/ejhg.2013.3. PubMed DOI PMC

Van Gennip AH. Defects in metabolism of purines and pyrimidines. Nederlands Tijdschrift voor Klinische Chemie. 1999;24:171–175.

Simmonds H, Reiter S, Nishino T. Hereditary xanthinuria. Orphanet Encyclopedia. 2003. https://www.researchgate.net/publication/285222077_Hereditary_xanthinuria. Accessed July 2016.

Reiter S, Simmonds HA, Zollner N, Braun SL, Knedel M. Demonstration of a combined deficiency of xanthine oxidase and aldehyde oxidase in xanthinuric patients not forming oxipurinol. Clin Chim Acta. 1990;187(3):221–234. doi: 10.1016/0009-8981(90)90107-4. PubMed DOI

Johnson JL, Duran M. Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular basis of inherited disease. 8. New York: McGraw-Hill; 2001. pp. 3163–3177.

Vijayakumar K, Gunny R, Grünewald S, Carr L, Chong KW, DeVile C, et al. Clinical neuroimaging features and outcome in molybdenum cofactor deficiency. Pediatr Neurol. 2011;45(4):246–252. doi: 10.1016/j.pediatrneurol.2011.06.006. PubMed DOI

Macaya A, Brunso L, Fernandez-Castillo N, Arranz JA, Ginjaar HB, Cuenca-Leon E, et al. Molybdenum cofactor deficiency presenting as neonatal hyperekplexia: a clinical, biochemical and genetic study. Neuropediatrics. 2005;36(06):389–394. doi: 10.1055/s-2005-872877. PubMed DOI

Van den Berghe G, Vincent MF, Marie S. Disorders of purine and pyrimidine metabolism. In: Fernandes J, Saudubray JM, van den Berghe G, Walter JH, editors. Inborn metabolic diseases. Springer: Berlin; 2006. pp. 433–449.

Raivio KO, Saksela M, Lapatto R. Xanthine oxidoreductase-role in human pathophysiology and in hereditary xanthinuria. In: Scriver CR, Baeudet Al, Sly WS, Valle D eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: Mc-Graw Hill; 2001. p. 2639-52.

Simoni RE, Gomes LNLF, Scalco FB, Oliveira CPH, Neto FRA, de Oliveira MLC. Uric acid changes in urine and plasma: an effective tool in screening for purine inborn errors of metabolism and other pathological conditions. J Inherit Metab Dis. 2007;30(3):295–309. doi: 10.1007/s10545-007-0455-8. PubMed DOI

Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, et al. Molecular identification of a renal urate-anion exchanger that regulates blood urate levels. Nature. 2002;417(6887):447–452. doi: 10.1038/nature742. PubMed DOI

Gabrikova D, Bernasovska J, Sokolova J, Stiburkova B. High frequency of SLC22A12 variants causing renal hypouricemia 1 in the Czech and Slovak Roma population; simple and rapid detection method by allele-specific polymerase chain reaction. Urolithiasis. 2015;43(5):441–445. doi: 10.1007/s00240-015-0790-4. PubMed DOI

Sebesta I, Stiburkova B, Bartl J, Ichida K, Hosoyamada M, Taylor J, et al. Diagnostic tests for primary renal hypouricemia. Nucleosides Nucleotides Nucleic Acids. 2011;30(12):1112–1116. doi: 10.1080/15257770.2011.611483. PubMed DOI

Matsuo H, Chiba T, Nagamori S, et al. Mutations in glucose transporter 9 gene SLC2A9 cause renal hypouricemia. Am J Hum Genet. 2008;83(6):744–751. doi: 10.1016/j.ajhg.2008.11.001. PubMed DOI PMC

Dinour D, Gray NK, Campbell S, Shu X, Sawyer L, Richardson W, et al. Homozygous SLC2A9 mutations cause severe renal hypouricemia. J Am Soc Nephrol. 2010;21(1):64–72. doi: 10.1681/ASN.2009040406. PubMed DOI PMC

Ohta T, Sakano T, Igarashi T, Itami N, Ogawa T, Group ARFAwRHR Exercise-induced acute renal failure associated with renal hypouricaemia: results of a questionnaire-based survey in Japan. Nephrol Dial Transpl. 2004;19(6):1447–1453. doi: 10.1093/ndt/gfh094. PubMed DOI

Jinnah HA, Friedmann T. Lesch–Nyhan disease and its variants. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001. p. 2537–60.

Torres RJ, Puig JG, Jinnah HA. Update on the phenotypic spectrum of Lesch–Nyhan disease and its attenuated variants. Curr Rheumatol Rep. 2012;14(2):189–194. doi: 10.1007/s11926-011-0231-5. PubMed DOI PMC

Jinnah HA. Lesch–Nyhan disease: from mechanism to model and back again. Dis Model Mech. 2009;2(3–4):116–121. doi: 10.1242/dmm.002543. PubMed DOI PMC