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Hyperammonemia with complex urinary tract anomaly: a case report
Hyperammonemia With Complex Urinary Tract Anomaly: A Case Report By H.O.S. Gabra, P.A. Fenton, J.R. Bonham, and A.E. Mackinnon Sheffield, England
Hyperammonemia has been reported rarely in the pediatric age group in systemically ill patients. All cases resulted from infections with urea splitting organisms, which are more common among patients who have undergone surgical procedures on the urinary tract. The authors report for the first time in the pediatric literature, one patient who presented with hyperammonemic encephalopathy that resulted from
urinary tract infection with Staphylococcus epidermidis and Corynebacterium sp. J Pediatr Surg 38:E58. © 2003 Elsevier Inc. All rights reserved.
CASE REPORT
ure conditions,1 urea cycle disorders, and, rarely, after therapeutic procedures on the urinary tract.2-5 Hyperammonemia results from either failure of metabolism of the ammonia by the hepatic mitochondria, which leads to impairment of the urea cycle, or from increase in the load of ammonia by the action of ureasplitting organisms on urea. Urinary infection with Proteus sp., Corynebacterium sp. and Staphylococcus aureus have been reported to be associated with hyperammonemic encephalopathy in children and adults.6,7 In our patient, renal tract surgery involving the use of implanted devices has predisposed to the infection with opportunistic organisms such as S. epidermidis and Corynebacterium sp. Although these 2 organisms are known to be urease producers,8 there are no reports of hyperammonemia in children resulting from urinary tract infection with them. Their action resulted in increased production and absorption of ammonia. Hyperammonemia leads to glutamine-mediated effects on the brain such as astrocytic swelling, cerebral edema, and raised intracranial pressure, which produce the clinical picture of encephalopathy.4 Despite initial equivocal biochemical results, no definite evidence of primary urea cycle disorder was found in our patient. This case is similar to other reports that suggest that some individuals have a genetic predisposi-
A
7-YEAR-OLD boy initially presented at the age of 15 months with severe bilateral hydroureter-hydronephrosis and subsequently underwent bilateral Y-ureterostomies. Further investigations excluded posterior urethtral valves as the etiology for his hydronephrosis, and confirmed the diagnosis of neurogenic bladder with multiple diverticula owing to spinal cord dysraphism. At the age of 7 years, he had surgical closure of his right ureterostomy over a double pigtail ureteric stent and was discharged home on prophylactic oral trimethoprim. At this time, urine microscopy and culture were clear. Six days postoperatively, he became unwell and returned as an emergency with vomiting, lethargy, and significantly impaired level of consciousness. Neurologic examination showed generalized hypotonia, increase in the deep tendon reflexes, and extensor plantar responses. He was admitted to the intensive care unit, and subsequent management with fluid restriction, intravenous mannitol, and hyperventilation resulted in a decrease in his intracranial pressure, which initially was 30 mm Hg. Results of blood tests including full blood count and renal and liver function tests all were within normal limits. Peak serum ammonia level was 269 mol/L (normal ⬍50 mol/L). Urine analysis showed the presence of Staphylococcus epidermidis and Corynebacterium species. Biochemical investigations including an allopurinol loading test showed peak orotate level 17.0 mol/mmol creatinine (reference ⬍13 mol/mmol creatinine) and peak orotidine level of 19.3 mol/mmol creatinine (reference 0.9 to 6.4 mol/mmol creatinine). These results were reported equivocal from 2 independent laboratories. A liver biopsy result showed normal activity for ornitine carbamyltransferase (OCT) and carbamyl-phosphate synthetase (CPS). Cystoscopy and subsequent removal of the pigtail stent was performed and culture yielded Corynebacterium sp. He responded to the above management, and his serum ammonia and intracranial pressure levels returned to normal limits within a week of admission; he was weaned off ventilation by the 25th day. Further recovery was slow, and he was discharged home after 10 weeks. Outpatient neurologic follow-up at 18 months showed improvement of his residual neurologic status, but he still showed global delay, speech deficit, and hypertonic weakness.
DISCUSSION
Hyperammonemia has been described in different clinical situations including in patients with hepatic fail-
16
INDEX WORDS: Hyperammonaemia, urinary tract infection, urea splitting organisms.
From the Paediatric Surgical Unit, and the Departments of Microbiology and Chemical Pathology and Neonatal Screening, Sheffield Children’s Hospital NHS Trust, Sheffield, UK. Address reprint requests to Mr Hany O.S. Gabra, FRCS, Research Fellow, Paediatric Surgical Unit, Sheffield Children’s Hospital NHS Trust, Western Bank, Sheffield, S10 2TH, UK. © 2003 Elsevier Inc. All rights reserved. 1531-5037/03/3811-0038$30.00/0 doi:10.1016/S0022-3468(03)000603-1
Journal of Pediatric Surgery, Vol 38, No 11 (November), 2003: E58
HYPERAMMONEMIA WITH COMPLEX URINARY TRACT ANOMALY
tion to the development of hyperammonemia without having a frank urea cycle disorder.9 Such individuals may not become symptomatic or hyperammonemic unless exposed to an excessive nitrogen overload and, in our case, this was associated with a urinary tract infection with organisms known to produce urease but previously not reported in this clinical context. Although in previous reports of similar cases, orotic acid levels were
17
noted as normal,4 the lack of precise serum levels in those reports makes interpretation and comparison with our case difficult. Our case shows the need for careful postoperative monitoring of patients who have had surgery on the urinary tract and that plasma ammonia levels should be measured if there is any clinical suspicion of hyperammonemia.
REFERENCES 1. Plauth M, Roske AE, Romaniuk P, et al: Post-feeding hyperammonaemia in patients with transjugular intrahepatic portosystemic shunt and liver cirrhosis: Role of small intestinal ammonia release and route of nutrient administration. Gut 46:849-855, 2000 2. Sinha B, Gonzalez R: Hyperammonemia in a boy with obstructive ureterocele and proteus infection. J Urol 131:330-331, 1984 3. Kiyokawa H, Igawa Y, Nishizawa O: Hyperammonaemic encephalopathy associated with retention of urine in multiple large diverticula. BJU International 88:122-123, 2001 4. Zuberi SM, Stephenson JB, Azmy AF, et al: Hyperammonaemic encephalopathy after a subureteric injection for vesicoureteric reflux. Arch Dis Child 79:363-364, 1998 5. Cheang HK, Rangecroft L, Plant ND, et al: Hyperammonaemia
due to klebsiella infection in a neuropathic bladder. Pediatric Nephrol 12:658-659, 1998 6. McEwan P, Simpson D, Kirk JM, et al: Short report: Hyperammonaemia in critically ill septic infants. Arch Dis Child 84:512-513, 2001 7. De Jonghe B, Janier V, Abderrahim N, et al: Urinary tract infection and coma. Lancet 360:996, 2002 8. Barrow GI, Feltham RKA: Cowan and Steel’s Manual for the Identification of Medical Bacteria (ed 3). Cambridge, Cambridge University Press, 1993 9. Bonham JR, Guthrie P, Downing M, et al: The allopurinol load test lacks specificity for primary urea cycle defects. J Inherit Metab Dis 22:174-184, 1999
Hyperammonemia has been reported rarely in the pediatric age group in systemically ill patients. All cases resulted from infections with urea splitting organisms, which are more common among patients who have undergone surgical procedures on the urinary tract. The authors report for the first time in the pediatric literature, one patient who presented with hyperammonemic encephalopathy that resulted from
urinary tract infection with Staphylococcus epidermidis and Corynebacterium sp. J Pediatr Surg 38:E58. © 2003 Elsevier Inc. All rights reserved.
CASE REPORT
ure conditions,1 urea cycle disorders, and, rarely, after therapeutic procedures on the urinary tract.2-5 Hyperammonemia results from either failure of metabolism of the ammonia by the hepatic mitochondria, which leads to impairment of the urea cycle, or from increase in the load of ammonia by the action of ureasplitting organisms on urea. Urinary infection with Proteus sp., Corynebacterium sp. and Staphylococcus aureus have been reported to be associated with hyperammonemic encephalopathy in children and adults.6,7 In our patient, renal tract surgery involving the use of implanted devices has predisposed to the infection with opportunistic organisms such as S. epidermidis and Corynebacterium sp. Although these 2 organisms are known to be urease producers,8 there are no reports of hyperammonemia in children resulting from urinary tract infection with them. Their action resulted in increased production and absorption of ammonia. Hyperammonemia leads to glutamine-mediated effects on the brain such as astrocytic swelling, cerebral edema, and raised intracranial pressure, which produce the clinical picture of encephalopathy.4 Despite initial equivocal biochemical results, no definite evidence of primary urea cycle disorder was found in our patient. This case is similar to other reports that suggest that some individuals have a genetic predisposi-
A
7-YEAR-OLD boy initially presented at the age of 15 months with severe bilateral hydroureter-hydronephrosis and subsequently underwent bilateral Y-ureterostomies. Further investigations excluded posterior urethtral valves as the etiology for his hydronephrosis, and confirmed the diagnosis of neurogenic bladder with multiple diverticula owing to spinal cord dysraphism. At the age of 7 years, he had surgical closure of his right ureterostomy over a double pigtail ureteric stent and was discharged home on prophylactic oral trimethoprim. At this time, urine microscopy and culture were clear. Six days postoperatively, he became unwell and returned as an emergency with vomiting, lethargy, and significantly impaired level of consciousness. Neurologic examination showed generalized hypotonia, increase in the deep tendon reflexes, and extensor plantar responses. He was admitted to the intensive care unit, and subsequent management with fluid restriction, intravenous mannitol, and hyperventilation resulted in a decrease in his intracranial pressure, which initially was 30 mm Hg. Results of blood tests including full blood count and renal and liver function tests all were within normal limits. Peak serum ammonia level was 269 mol/L (normal ⬍50 mol/L). Urine analysis showed the presence of Staphylococcus epidermidis and Corynebacterium species. Biochemical investigations including an allopurinol loading test showed peak orotate level 17.0 mol/mmol creatinine (reference ⬍13 mol/mmol creatinine) and peak orotidine level of 19.3 mol/mmol creatinine (reference 0.9 to 6.4 mol/mmol creatinine). These results were reported equivocal from 2 independent laboratories. A liver biopsy result showed normal activity for ornitine carbamyltransferase (OCT) and carbamyl-phosphate synthetase (CPS). Cystoscopy and subsequent removal of the pigtail stent was performed and culture yielded Corynebacterium sp. He responded to the above management, and his serum ammonia and intracranial pressure levels returned to normal limits within a week of admission; he was weaned off ventilation by the 25th day. Further recovery was slow, and he was discharged home after 10 weeks. Outpatient neurologic follow-up at 18 months showed improvement of his residual neurologic status, but he still showed global delay, speech deficit, and hypertonic weakness.
DISCUSSION
Hyperammonemia has been described in different clinical situations including in patients with hepatic fail-
16
INDEX WORDS: Hyperammonaemia, urinary tract infection, urea splitting organisms.
From the Paediatric Surgical Unit, and the Departments of Microbiology and Chemical Pathology and Neonatal Screening, Sheffield Children’s Hospital NHS Trust, Sheffield, UK. Address reprint requests to Mr Hany O.S. Gabra, FRCS, Research Fellow, Paediatric Surgical Unit, Sheffield Children’s Hospital NHS Trust, Western Bank, Sheffield, S10 2TH, UK. © 2003 Elsevier Inc. All rights reserved. 1531-5037/03/3811-0038$30.00/0 doi:10.1016/S0022-3468(03)000603-1
Journal of Pediatric Surgery, Vol 38, No 11 (November), 2003: E58
HYPERAMMONEMIA WITH COMPLEX URINARY TRACT ANOMALY
tion to the development of hyperammonemia without having a frank urea cycle disorder.9 Such individuals may not become symptomatic or hyperammonemic unless exposed to an excessive nitrogen overload and, in our case, this was associated with a urinary tract infection with organisms known to produce urease but previously not reported in this clinical context. Although in previous reports of similar cases, orotic acid levels were
17
noted as normal,4 the lack of precise serum levels in those reports makes interpretation and comparison with our case difficult. Our case shows the need for careful postoperative monitoring of patients who have had surgery on the urinary tract and that plasma ammonia levels should be measured if there is any clinical suspicion of hyperammonemia.
REFERENCES 1. Plauth M, Roske AE, Romaniuk P, et al: Post-feeding hyperammonaemia in patients with transjugular intrahepatic portosystemic shunt and liver cirrhosis: Role of small intestinal ammonia release and route of nutrient administration. Gut 46:849-855, 2000 2. Sinha B, Gonzalez R: Hyperammonemia in a boy with obstructive ureterocele and proteus infection. J Urol 131:330-331, 1984 3. Kiyokawa H, Igawa Y, Nishizawa O: Hyperammonaemic encephalopathy associated with retention of urine in multiple large diverticula. BJU International 88:122-123, 2001 4. Zuberi SM, Stephenson JB, Azmy AF, et al: Hyperammonaemic encephalopathy after a subureteric injection for vesicoureteric reflux. Arch Dis Child 79:363-364, 1998 5. Cheang HK, Rangecroft L, Plant ND, et al: Hyperammonaemia
due to klebsiella infection in a neuropathic bladder. Pediatric Nephrol 12:658-659, 1998 6. McEwan P, Simpson D, Kirk JM, et al: Short report: Hyperammonaemia in critically ill septic infants. Arch Dis Child 84:512-513, 2001 7. De Jonghe B, Janier V, Abderrahim N, et al: Urinary tract infection and coma. Lancet 360:996, 2002 8. Barrow GI, Feltham RKA: Cowan and Steel’s Manual for the Identification of Medical Bacteria (ed 3). Cambridge, Cambridge University Press, 1993 9. Bonham JR, Guthrie P, Downing M, et al: The allopurinol load test lacks specificity for primary urea cycle defects. J Inherit Metab Dis 22:174-184, 1999