Kelley-Seegmiller syndrome as cause of recurrent acute kidney injury in 9-year-old boy
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Oddział Dziecięcy, Szpital Międzyrzecki Sp. z o.o., Międzyrzecz
Zakład Biochemii, Katedra Biochemii i Chemii Medycznej, Pomorski Uniwersytet Medyczny, Szczecin
Zakład Chemii Medycznej, Katedra Biochemii i Chemii Medycznej, Pomorski Uniwersytet Medyczny, Szczecin
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Tomasz Jarmoliński   

Oddział Dziecięcy, Szpital Międzyrzecki Sp. z o.o., ul. Konstytucji 3 Maja 35, 66-300 Międzyrzecz
Ann. Acad. Med. Siles. 2017;71:116-121
Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is the second most common, after xanthinuria, inherited defect of purine metabolism. Described in 1967 in patients with gout and nephrolithiasis, the Kelley-Seegmiller syndrome is caused by HPRT partial deficiency. A complete lack of enzyme activity leads to additional severe neurobehavioral symptoms with self-mutilation creating clinical a picture known since 1964 as the Lesh-Nyhan syndrome. Enzymatic and molecular analyses useful for precise diagnosis are not routinely available in Poland, so the prevalence of HPRT defects is very low. Here we presented a case of a 9-year-old boy suffering from recurrent acute kidney injury (4 episodes) with diagnosis of the Kelley-Seegmiller syndrome based on the clinical picture and simple laboratory tests confirmed by evaluation of HPRT enzyme activity.
Jurecka A. Wrodzone wady metabolizmu puryn i pirymidyn. Postępy Biochem. 2011; 57: 172–182.
Fathallah-Shaykh S., Cramer M. Uric acid and the kidney. Pediatr. Nephrol. 2014; 29: 999–1008.
Torres R.J., Puig J.G. Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. Orphanet J. Rare Dis. 2007; 2: 48. DOI:10.1186/1750-1172-2-48;
Catel W., Schmidt J. Über familiäre gichtische Diathese in Verbindung mit zerebralen und renalen Symptomen bei einem Kleinkind. Deutsch. Med. Wchnschr. 1959; 84: 2145–2147.
Lesch M., Nyhan W.L. A familial disorder of uric acid metabolism and central nervous system function. Am. J. Med. 1964; 36: 561–570.
Seegmiller J.E., Rosenbloom F.M., Kelley W.N. Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 1967; 155: 1682–1684.
Kelley W.N., Rosenbloom F.M., Henderson J.F., Seegmiller J.E. A specific enzyme defect in gout associated with overproduction of uric acid. Proc. Natl. Acad. Sci. USA 1967; 57: 1735–1739.
Page T., Nyhan W.L. The spectrum of HPRT deficiency: an update. Adv. Exp. Med. Biol. 1989; 253A: 129–133.
Puig J.G., Torres R.J., Mateos F.A., Ramos T.H., Arcas J.M., Buño A.S., O'Neill P. The spectrum of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Clinical experience based on 22 patients from 18 Spanish families. Medicine 2001; 80: 102–112.
Jinnah H.A., Friedmann T. Lesh-Nyhan disease and its variants. W: Scriver C.R., Beaudet A.L., Sly W.S., Valle D. The metabolic and molecular basis of inherited disease. McGraw Hill. New York 2000, s. 2537–2570.
Jolly D.J., Esty A.C., Bernard H.U., Friedmann T. Isolation of a genomic clone partially encoding human hypoxanthine phosphoribosyltransferase. Proc. Natl. Acad. Sci. USA 1982; 79: 5038–5041.
Official website of the Lesh-Nyhan disease Study Group: [dostęp: 17.02.2017].
Jinnah H.A., De Gregorio L., Harris J.C., Nyhan W.L., O’Neil P. The spectrum of inherited mutations causing HPRT deficiency: 75 new cases anda review of 196 previously reported cases. Mutation Research 2000; 463: 309–326.
Torres R.J., Puig J.G. Hypoxanthine deregulates genes involved in early neuronal development. Implication in Lesh-Nyhan pathogenesis. J. Inherit. Metabolic. Dis. 2015; 38: 1109–1118.
Jurecka A., Popowska E., Tylki-Szymańska A., Kubalska J., Ciara E., Krumina Z., Sykut-Cegielska J., Pronicka E. Deficyt fosforybozylotransfe-razy hipoksantynoguaninowej – kliniczna, biochemiczna oraz molekularna charakterystyka pacjentów. Przegląd Pediatryczny 2008; 38: 227–236.
Cameron J.S., Moro F., Simmonds H.A. Gout, uric acid and purine metabolism in pediatric nephrology. Pediatr. Nephrol. 1993; 7: 105–118.
Ma A., Shroff R., Marks S.D. An unusual case of renal failure: Que-stions. Pediatr. Nephrol. 2017; 32: 77–78.
Ma A., Shroff R., Marks S.D. An unusual case of renal failure: Answers. Pediatr. Nephrol. 2017; 32: 79–80.
van Dael C.M., Pierik L.J., Reijngoud D.J., Niezen-Koning K.E., van Diggelen O.P., van Spronsen F.J. Partial hypoxanthine-guanine phosphoribosyl transferase deficiency without elevated urinary hypoxanthine excretion. Mol. Genet. Metab. 2007; 90: 221–223.
Kassimatis T.I., Simmonds H.A., Goudas P.C., Marinaki A.M., Fairbanks L.D., Diamandopoulos A.A. HPRT deficiency as the cause of ESRD in a 24-year-old patient: a very rare presentation of the disorder. J. Nephrol. 2005; 18: 447–451.
Kłosowska A., Giżewska M., Blachowska E., Batko T., Wierzba J. Zespół Lesha-Nyhana – opóźnienie rozwoju psychoruchowego o nietypowym przebiegu klinicznym. Trudności diagnostyczne. Forum Medycyny Rodzinnej 2015; 9: 416–421.
Torres R.J., Puig J.G. The diagnosis of HPRT deficiency in the 21st century. Nucleosides Nucleotides Nucleic Acids 2008; 27: 564–569.
Bell S., Kolobova I., Crapper L., Ernst C. Lesh-Nyhan Syndrome: Models, Theories and Therapies. Mol. Syndromol. 2016; 7: 302–311.
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