1/9. 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.- - - - - - - - - - ranking = 1keywords = hyperammonemia (Clic here for more details about this article) |
2/9. urea cycle disorders in Thai infants: a report of 5 cases.urea Cycle Disorders (UCD) is an inborn error of urea synthesis in which ammonium and other nitrogenous precursors of urea accumulate leading to episodic coma and a high mortality rate. Therapy with peritoneal dialysis, essential amino acids or their nitrogen-free analogues has increased survival. The authors report 5 cases of urea cycle disorders, all of whom developed and were rescued from hyperammonemic coma. However, the eventual outcome was quite variable. argininosuccinate lyase deficiency (ALD) Case 1. A 2 month old male infant, a product of a consanguineous marriage (Suphanburi province); developed poor feeding on day 7, lethargy, convulsion, hepatomegaly and respiratory alkalosis leading to respiratory failure and coma. hyperammonemia, elevation of glutamic acid and argininosuccinic acid and its anhydrides confirmed the diagnosis of ALD. He is now 9 years old and severely retarded. Case 2. A male infant with history of lethargy, poor feeding on day 3, treated as sepsis and required respiratory support for 6 days; subsequently readmitted at age 2 weeks with vomitting, lethargy, seizure activity and hyperammonemia, and was treated by a local pediatrician in Songkhla province. There was a history of parental consanguinity and he was referred to Siriraj Hospital on day 64 with severe essential amino acid deficiency and acrodermatitis enteropathica with markedly elevated plasma citrulline level. In spite of aggressive treatment; the patient developed sepsis and he expired on day 78. ornithine transcarbamylase deficiency (OTC) Case 3. An eleven-month-old male infant, the product of a non-consanguineous marriage, developed neonatal onset of hyperammonemia on day 5 after poor feeding, lethargy, hypothermia, seizure, apnea and coma. He was rescued from neonatal hyperammonemic coma on day 9 after aggressive treatment, but expired at eleven months of age after overwhelming sepsis. Case 4. A male infant, sibling of case 3 was referred to Siriraj Hospital on day 8 with hyperammonemia and coma. In spite of intensive genetic counseling given after the birth of their first child with OTC, the couple chose to have another baby without informing any physician. The baby developed vomiting and lethargy on day 2; subsequently hyperammonemia was noted. In spite of aggressive treatment given; hepatic dysfunction, renal failure and disseminated intravascular coagulation defects occurred on day 15. He expired on day 18 after parental permission for discontinuation of all treatment. Argininosuccinate synthetase deficiency (ASS) or citrullinemia. Case 5. A seven week old female infant, the product of a consanguineous marriage and of Pakistani ethnic origin; developed intermittent vomiting from day 6. Initial diagnoses included ruminations, sepsis and pyloric stenosis for which she was operated on (day 30); however, vomiting continued; subsequently seizures, hyperammonemic coma developed and she was rescued from hyperammonemic coma within 30 hours. Significant elevations of citrulline and L-glutamine were demonstrated. She was discharged in excellent condition to her home in Dubai, the united arab emirates.- - - - - - - - - - ranking = 1keywords = hyperammonemia (Clic here for more details about this article) |
3/9. brain MR imaging in neonatal hyperammonemic encephalopathy resulting from proximal urea cycle disorders.We present brain MR images in three patients with neonatal-onset hyperammonemic encephalopathy resulting from urea-cycle disorders (two sisters with deficiency of the carbamyl phosphate synthetase I reaction step and one boy with an ornithine transcarbamylase deficiency). MR imaging revealed almost identical findings of injury to the bilateral lentiform nuclei and the deep sulci of the insular and perirolandic regions; to our knowledge, this pattern has not been previously reported. We hypothesize that these lesions presumably reflect the distribution of brain injury due to hypoperfusion secondary to hyperammonemia and hyperglutaminemia in the neonatal period.- - - - - - - - - - ranking = 0.25keywords = hyperammonemia (Clic here for more details about this article) |
4/9. Intermittent hyperammonemic encephalopathy in a child with ornithine transcarbamylase deficiency.ornithine transcarbamylase (OTC) deficiency is an X-linked disorder and the most common inherited cause of hyperammonemia. Clinical manifestations are more severe in hemizygous males who often present in neonatal period. Heterozygous females may be asymptomatic until juvenile or adulthood. Fluctuating concentration of ammonia, glutamine and other excitotoxic amino acids result in a chronic or episodically recurring encephalopathy. The authors report a heterozygous female with OTC deficiency who presented with recurrent encephalopathy.- - - - - - - - - - ranking = 0.25keywords = hyperammonemia (Clic here for more details about this article) |
5/9. A patient with propionic acidemia managed with continuous insulin infusion and total parenteral nutrition.An infant newly diagnosed with propionic acidemic coma was managed successfully with total parenteral nutrition (TPN) and continuous infusion of insulin. The urinary excretion of 3-hydroxypropionic acid was reduced to 3% of the admission value in 4 days, gradually decreasing to 1.5% in 16 days. The treatment did not prevent a prolonged episode of thrombocytopenia. The infant tolerated TPN well, except for continued hyper-lactic acidemia (2 to 4 times normal). Metabolic acidosis and mild hyperammonemia recurred only when the patient had sepsis secondary to candida albicans and staphylococcus aureus infection.- - - - - - - - - - ranking = 0.25keywords = hyperammonemia (Clic here for more details about this article) |
6/9. Periodic hyperammonemic encephalopathy associated with a ureterosigmoidostomy.Ureterosigmoidostomy, a urinary diversion procedure performed for treatment congenital urologic defects or bladder cancer, may be associated with hyperammonemia. A delayed periodic encephalopathy, characterized by dysarthria, ataxia, and coma, developed in a 44-year-old woman who had undergone this procedure. hyperammonemia-associated neurotoxicity resolved after surgical revision of the ureterosigmoidostomy to a uretero-ileostomy. Therefore, a treatable episodic encephalopathy may occur in association with hyperammonemia in patients who have undergone ureterosigmoidostomy.- - - - - - - - - - ranking = 0.5keywords = hyperammonemia (Clic here for more details about this article) |
7/9. Unusual biochemical and clinical features in a girl with ornithine transcarbamylase deficiency.A girl, ultimately diagnosed as having profound ornithine transcarbamylase (OTC) deficiency, presented as a neonate with feeding intolerance, irritability, and seizures without concurrent hyperammonemia. Developing normally until ten months of age, the girl subsequently experienced two episodes of hyperammonemia, which were associated with focal seizures and residual hemiparesis. She continued to have profound neurologic impairment and seizures and died at 26 months of age, despite appropriate dietary protein restriction, sodium benzoate, and arginine supplementation. Symptomatic OTC deficiency has not been previously reported unassociated with hyperammonemia. The recurrent cerebrovascular episodes are distinctly uncommon in patients with urea cycle enzymopathies.- - - - - - - - - - ranking = 0.75keywords = hyperammonemia (Clic here for more details about this article) |
8/9. Clinical features of carbamyl phosphate synthetase-I deficiency in an adult.carbamyl phosphate synthetase-I (CPS-I) catalyzes the first reaction required for the conversion of ammonia to urea through the urea cycle. Severe CPS-I deficiency causes marked hyperammonemia with encephalopathy in infancy and usually results in death within the first few months of life. We describe a 33-year-old woman whose CPS-I activity is less than 5% of normal. She has had mild, intermittent symptoms throughout life but has never experienced severe encephalopathy. Although mildly retarded, she has no major neurological deficits. Therapy with a low-protein diet, lactulose, and sodium benzoate has prevented recurrence of hyperammonemia and symptoms. Cranial computed tomographic scans demonstrate prominent lucency of cerebral white matter, and cerebral evoked potential recordings indicate slowed central conduction. These findings suggest that the metabolic disturbances in this patient may have adversely affected central myelin formation or maintenance. This woman represents, to our knowledge, the oldest reported patient with CPS-I deficiency, and the case illustrates the need to consider urea cycle disorders in the differential diagnosis of intermittent neurological symptoms regardless of the patient's age.- - - - - - - - - - ranking = 0.5keywords = hyperammonemia (Clic here for more details about this article) |
9/9. ornithine transcarbamylase deficiency in females: an often overlooked cause of treatable encephalopathy.ornithine transcarbamylase deficiency is an X-linked recessive disorder of urea biosynthesis characterized by recurrent, often fatal, hyperammonemic encephalopathy in affected males; carrier females are usually asymptomatic. We report here the clinical and laboratory findings in five symptomatic heterozygous females with ornithine transcarbamylase deficiency. In each case, the onset of symptoms occurred in the 1st year of life, but diagnosis was delayed by up to 15 years. Symptoms included recurrent vomiting with lethargy (five patients), dietary protein intolerance (five), irritability (four), severe acute encephalopathy (three), ataxia (three), and acute hemiparesis (two). All eventually showed evidence of developmental delay or learning difficulties. Two of the three who experienced severe, acute, hyperammonemic encephalopathy suffered serious, permanent neurologic sequelae. Three of the patients showed decreased ornithine transcarbamylase activity in liver obtained by needle biopsy, and the other two had marked orotic aciduria associated with hyperammonemia. neuroimaging studies demonstrated persistent abnormal lobar attenuation and abnormal signal on computed tomographic scan and magnetic resonance imaging. All patients showed marked symptomatic improvement on treatment with dietary protein restriction supplemented by pharmacologic measures to increase nonprotein nitrogen excretion. ornithine transcarbamylase deficiency should be considered in the differential diagnosis of acute or chronic encephalopathy in females at any age.- - - - - - - - - - ranking = 0.25keywords = hyperammonemia (Clic here for more details about this article) |