Autori prezentujú vzácnu kazuistiku novorodenca s toxickou dyspepsiou, extrémnou hyperurikémiou (2000 µmol/l) a akútnou renálnou insuficienciou (ARI). Pre oligoanúriu a vysoké uremické parametre indikovali peritoneálnu dialýzu, ktorá viedla k úprave azotémie a obnoveniu diurézy. Hyperurikémia (700–800 µmol/l) perzistovala aj po zlepšení obličkových funkcií (GFR 31ml/min; s-kreatinín 71 µmol/l), preto sa v diagnostike zamerali na zistenie príčiny hyperurikémie. Zistili zvýšenú renálnu exkréciu purínov a signifikantne zníženú aktivitu hypoxantínguanínfosforibozyltransferázy (HPRT) v erytrocytoch. Molekulovo-genetickou analýzou génu pre HPRT bola zistená doteraz v literatúre neopísaná zostrihová mutácia v intróne 1 (c.27+2T>C). Pacient dovŕšil 1 rok, má oneskorený psychomotorický vývoj s dyskinézami. Renálne funkcie sú stabilizované, ale hyperurikémia pretrváva aj pri liečbe alopurinolom, USG nález obličiek progreduje (redukcia parenchýmu a hrudkovité kalcifikáty). Autori predpokladajú kauzálnu súvislosť medzi ARI v novorodeneckom období (akútna urátová nefropatia) a Leschovým-Nyhanovým syndrómom. Kazuistika je tretím publikovaným prípadom novorodenca s ARI a dedičnou poruchou syntézy purínov. U detí s hyperurikémiou vždy treba myslieť aj na DPM purínov a pri dôkaze nadprodukcie kyseliny močovej v tele indikovať enzymatické vyšetrenie.

Inborn error of metabolism (IEM) of purines associated with hyperuricemia is a rare cause of acute renal failure in childhood. It could be caused by a mutation in hypoxanthin- guanin-phosphoribosyl-transferase (HPRT) gene, leading to over production of uric acid and hyperuricosuria. Lesch-Nyhan syndrome (LNS) is an X-linked disease caused by complete deficiency of HPRT activity, while partial HPRT deficiency is termed Kelley-Seegmiller syndrome. LNS mainly affects the kidney – as acute and chronic urate nephropathy and urolithiasis, joints – gouty arthritis, and nervous system. Neurological symptoms include mental retardation, dystonia, spasticity, hyperreflexia. Psychiatric features could be serious and include self-mutilation tendency. Prognosis is bad. Authors present a newborn boy with extreme hyperuricemia and acute renal failure (ARF), as a rare manifestation of IEM of purines. The 2 week-old boy was admitted with ARF, toxic dyspepsia and extreme hyperuricemia 2000 µmol/l. Due to oligo/anuria, creatinine 526 µmol/l, and glomerular filtration rate (GFR) 3.7 ml/min, acute peritoneal dialysis was indicated. This treatment led to an improvement of laboratory and clinical parameters. However, despite of the renal functions restoration (GFR 50 ml/min), hyperuricemia 700–800 µmol/l persisted. They excluded secondary causes of hyperuricemia; also high Kaufman index indicated overproduction of uric acid. For suspicion of purine IEM they estimated purine metabolites in urine and blood and enzyme activity of HPRT. The results reflected severe deficit of HPRT activity. Authors identified a novel mutation in intron 1 (c.27+2T>C) in the HPRT encoding gene. At present, the patient is one year old, with delayed psychomotor development and dystonia. Kidney ultrasound shows progression of renal impairment – reduction of renal parenchyma and calcifications. The authors assume causality between ARF in newborn period (acute urate nephropathy) and diagnosis of purine IEM – severe deficiency of HPRT activity (Lesch-Nyhan syndrome). For managing the children with hyperuricemia, it is essential also to think about the possibility of a purine-metabolism disorder and to include the investigation of purine metabolism in differential diagnostic procedures.

1 Klinika detí a dorastu LF UPJŠ a DFN Košice

Acute renal failure in newborn period – initial symptom of inborn error of metabolism of purines

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