| We report a patient with multiple myeloma who suffered from hyperammonemia after a second stem cell autograft. This syndrome is not well known but is associated with a high mortality rate. Considering the possibility of this diagnosis in patients developing confusion and neurological degradation with respiratory alkalosis after intensive chemotherapy, could allow earlier treatment and perhaps improved survival. Possible mechanisms and potential therapies are discussed. With rapid recognition and treatment of the syndrome, the patient fully recovered. One and a half years later, she is still alive and well, on interferon for persisting myeloma. ( info) |
2/80. Intravenous ribavirin and hyperammonemia in an immunocompromised patient infected with adenovirus. ribavirin is a synthetic guanosine analog with activity against dna and rna viruses. It was studied in human trials, and no marked adverse effect was reported beyond the potential for teratogenicity and reversible mild anemia. An 8-year-old girl received a multivisceral transplant and developed adenoviral pneumonia. She was treated with intravenous ribavirin and became hyperammonemic. Discontinuation of ribavirin led to a decrease in ammonia levels. This pattern was repeated when the drug was restarted and discontinued. We hypothesize that in a toxic environment the interaction of ribavirin with hepatocellular mitochondrial enzymes may lead to hyperammonemia. ( info) |
3/80. Continuous arteriovenous hemodiafiltration in the acute treatment of hyperammonaemia due to ornithine transcarbamylase deficiency. BACKGROUND: Acute hyperammonemia caused by urea cycle disorder is a medical emergency for which immediate managements should be taken to minimize permanent brain damage. Among different enzyme defects, ornithine transcarbamylase deficiency (OTC) is one of the most common enzyme defect in urea cycle disorders. We utilized continuous renal replacement therapy techniques in the acute treatment of hyperammonemia due to ornithine transcarbamylase deficiency. patients AND methods: Three male neonates with elevated serum ammonia levels were shown, based on urine organic acid analysis and serum amino acid studies, to have OTC deficiency. Administration of sodium benzoate and sodium phenylacetate for activating alternative nitrogen waste pathway were used associated with protein restriction. Other modalities, including blood exchange transfusion, peritoneal dialysis, continuous renal replacement therapy were utilized in an attempt to lower serum ammonia concentration. RESULTS: We report the successful use of continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), continuous arteriovenous hemodiafiltration (CAVHDF) in the acute management of hyperammonemia due to OTC deficiency. We also compared the ammonia clearance between peritoneal dialysis, exchange transfusion, CAVH, CAVHD and CAVHDF. It demonstrated the evidence that CAVHDF provides the best ammonia clearance. CONCLUSION: Continuous renal replacement therapy including CAVH, CAVHD, and CAVHDF may be the alternative techniques for acute management of hyperammonemia in inborn error of metabolism when dialysis machine is not available. Our data suggests CAVHDF provides the best ammonia clearance. ( info) |
4/80. A 6-year-old boy with hyperammonaemia: partial N-acetylglutamate synthase deficiency or portosystemic encephalopathy? We describe a 6-year-old boy admitted with lethargy and somnolence. Laboratory tests showed hyperammonaemia (arterial level 186 micromol/l) and slightly elevated prothrombin time. The patient was treated with sodium benzoate, lactulose and a protein-restricted diet. This resulted in an insufficient decrease in blood ammonia levels. Metabolic investigations were unrevealing apart from a slightly elevated urinary glutamine concentration. Liver tissue showed steatosis and mildly decreased activity of N-acetylglutamate synthase suggesting partial deficiency. Treatment with N-carbamyl glutamate did not affect serum ammonia levels. Colour Doppler sonography and MR angiography demonstrated a patent ductus venosus. After surgical ligation of the ductus venosus, serum ammonia levels returned to normal and mental and motor performance improved markedly. CONCLUSION: In late onset hyperammonaemia, partial N-acetylglutamate synthase deficiency and portocaval shunt should be ruled out. ( info) |
| Portal-systemic encephalopathy may be seen with hyperammonemia that complicates chronic liver disease. We report an unusual case of reversible parkinsonism associated with hyperammonemia and portal vein thrombosis. An active 90-year-old male developed motor slowing and resting hand tremor over 6 months. Examination showed asterixis, bradykinesia, cogwheel rigidity, rest tremor, and a parkinsonian gait. serum venous ammonia was elevated at 145 microM. The next day, the patient became comatose and serum ammonia was 178 microM. With lactulose therapy, serum ammonia level normalized and examination showed only minimal parkinsonism after 1 week. An abdominal CT scan identified portal vein thrombosis with porto-systemic shunting that reversed after 7 months of treatment. Examination 2 years later showed no signs of parkinsonism. Parkinsonism can dominate the clinical picture of patients with hyperammonemia before the onset of encephalopathy. ( info) |
| OBJECTIVE: Because the hyperinsulinism/hyperammonemia (HI/HA) syndrome is associated with gain of function mutations in the leucine-stimulated insulin secretion pathway, we examined whether protein feeding or fasting was responsible for hypoglycemia in affected patients. STUDY DESIGN: patients with HI/HA (8 children and 6 adults) were studied. All had dominantly expressed mutations of glutamate dehydrogenase and plasma concentrations of ammonium that were 2 to 5 times normal. The responses to a 24-hour fasting test were determined in 7 patients. Responses to a 1.5 gm/kg oral protein tolerance test in 12 patients were compared with responses of 5 control subjects. RESULTS: The median age at onset of hypoglycemia in the 14 patients was 9 months; diagnosis was delayed beyond age 2 years in 6 patients, and 4 were not given a diagnosis until adulthood. fasting tests revealed unequivocal evidence of hyperinsulinism in only 1 of 7 patients. Three did not develop hypoglycemia until 12 to 24 hours of fasting; however, all 7 demonstrated inappropriate glycemic responses to glucagon that were characteristic of hyperinsulinism. In response to oral protein, all 12 patients with HI/HA showed a fall in blood glucose compared with none of 5 control subjects. Insulin responses to protein loading were similar in the patients with HI/HA and control subjects. CONCLUSION: The postprandial blood glucose response to a protein meal is more sensitive than prolonged fasting for detecting hypoglycemia in the HI/HA syndrome. ( info) |
7/80. carbamyl phosphate synthetase 1 deficiency: a destructive encephalopathy. carbamyl phosphate synthetase I is a urea cycle enzyme. Severe deficiency of carbamyl phosphate synthetase I presents in the neonatal period as hyperammonemic encephalopathy with altered consciousness and occasional seizures after feeding begins. Episodes of altered consciousness with or without seizures and focal neurologic deficits are seen later with patients of partial carbamyl phosphate synthetase I deficiency. Fatal cerebral edema with brain herniation may develop on occasion. Three patients presenting with carbamyl phosphate synthetase I deficiency are reported with neuroimaging and pathologic findings illustrating the destructive encephalopathy with acute cerebral edema, followed by diffuse cerebral atrophy and occasional cystic encephalomalacia. The deterioration in carbamyl phosphate synthetase I deficiency occurs during the hyperammonemic crises. This deficiency may be difficult to treat despite the current advances in treatment strategies, especially in neonatal-onset patients with low carbamyl phosphate synthetase I activity. ( info) |
8/80. hyperammonemia in urea cycle disorders: role of the nephrologist. hyperammonemia associated with inherited disorders of amino acid and organic acid metabolism is usually manifested by irritability, somnolence, vomiting, seizures, and coma. Although the majority of these patients present in the newborn period, they may also present in childhood, adolescence, and adulthood with failure to thrive, persistent vomiting, developmental delay, or behavioral changes. Persistent hyperammonemia, if not treated rapidly, may cause irreversible neuronal damage. After the diagnosis of hyperammonemia is established in an acutely ill patient, certain diagnostic tests should be performed to differentiate between urea cycle defects and other causes of hyperammonemic encephalopathy. In a patient with a presumed inherited metabolic disorder, the aim of therapy should be to normalize blood ammonia levels. Recent experience has provided treatment guidelines that include minimizing endogenous ammonia production and protein catabolism, restricting nitrogen intake, administering substrates of the urea cycle, administering compounds that facilitate the removal of ammonia through alternative pathways, and, in severe cases, dialysis therapy. Initiation of dialysis in the encephalopathic patient with hyperammonemia is indicated if the ammonia blood level is greater than three to four times the upper limit of normal. Hemodialysis is the most effective treatment for rapidly reducing blood ammonia levels. Continuous hemofiltration and peritoneal dialysis are also effective modalities for reducing blood ammonia levels. An improved understanding of the metabolism of ammonia and neurological consequences of hyperammonemia will assist the nephrologist in providing optimal care for this high-risk patient population. ( info) |
| We report a case of alstrom syndrome with evidence of extensive hepatic disease diagnosed at five years of age, who subsequently developed acute liver failure and died at eight years of age. Such a case, with the patient dying before the age of ten, has not been described before. The biochemical findings during our patient's liver failure raised the question of a possible mitochondrial function defect in this syndrome. Further investigation of this possibility is needed. ( info) |
10/80. Short report: Hyperammonaemia in critically ill septic infants. Three infants with subphrenic abscess, pyonephrosis, and obstructive ureterocoele respectively had grossly increased concentrations of plasma ammonia. This was considered to be a result of infections with urea splitting organisms. All died in spite of intensive care support, including specific measures to reduce plasma ammonia. ( info) |