Diagnosis Of Hyperammonemia Research Articles

Diagnostic and Prognostic Value of Hyperammonemia in Patients with Liver Cirrhosis, Hepatic Encephalopathy, and Sarcopenia (Experts’ Agreement)

Introduction. In cirrhotic patients, hyperammonemia develops due to impaired ammonia detoxification and portosystemic blood shunting and is most commonly associated with hepatic encephalopathy and sarcopenia. Currently, there are questions regarding the diagnosis of hyperammonemia and the effect of ammonia-lowering therapy on disease outcomes.Materials and methods. The Russian Scientific Liver Society selected a panel of seven experts in liver cirrhosis research and management of patients with this disease to make reasoned statements and recommendations on the issue of diagnostic and prognostic value of hyperammonemia in patients with liver cirrhosis, hepatic encephalopathy and sarcopenia.Results. The Delphi panel identified the most relevant topics, in the form of PICO questions (patient or population, intervention, comparison, outcome). The Delphi panel made six questions relevant to clinical practice and gave reasoned answers, framed as ‘clinical practice recommendations and statements’ with evidence-based comments. The questions and statements were based on the search and critical analysis of medical literature by keywords in Englishand Russian-language databases. The formulated questions could be combined into four categories: hepatic encephalopathy, sarcopenia, hyperammonemia, and ammonia-lowering therapy.Conclusions. The results of the experts' work are directly relevant to the quality management of patients with liver cirrhosis, and their recommendations and statements can be used in clinical practice.

An Investigation of PS-b-PEO Polymersomes for the Oral Treatment and Diagnosis of Hyperammonemia.

Ammonia-scavenging transmembrane pH-gradient poly(styrene)-b-poly(ethylene oxide) polymersomes are investigated for the oral treatment and diagnosis of hyperammonemia, a condition associated with serious neurologic complications in patients with liver disease as well as in infants with urea cycle disorders. While these polymersomes are highly stable in simulated intestinal fluids at extreme bile salt and osmolality conditions, they unexpectedly do not reduce plasmatic ammonia levels in cirrhotic rats after oral dosing. Incubation in dietary fiber hydrogels mimicking the colonic environment suggests that the vesicles are probably destabilized during the dehydration of the intestinal chyme. The findings question the relevance of commonly used simulated intestinal fluids for studying vesicular stability. With the encapsulation of a pH-sensitive dye in the polymersome core, the local pH increase upon ammonia influx could be exploited to assess the ammonia concentration in the plasma of healthy and cirrhotic rats as well as in other fluids. Due to its high sensitivity and selectivity, this polymersome-based assay could prove useful in the monitoring of hyperammonemic patients and in other applications such as drug screening tests.

Hyperammonemia in a patient with obstructive urinary tract infection due to Corynebacterium urealyticum

Abstract A 93-year-old woman with neurogenic bladder was admitted to our hospital because of impaired consciousness. Her urine culture revealed urease-test-positive Corynebacterium urealyticum. She was diagnosed with hyperammonemia due to an obstructive urinary tract infection that was caused by urease-producing bacteria. The patient showed rapid improvement of impaired consciousness and hyperammonemia after urine analysis. It is necessary to consider obstructive urinary tract infection as a differential diagnosis of hyperammonemia, which commonly occurs in urinary tract infections owing to the presence of urease-producing bacteria. Relief from obstruction is the most important treatment for hyperammonemia caused by this mechanism.

Acute fatal presentation of ornithine transcarbamylase deficiency in a previously healthy male

Ornithine transcarbamylase (OTC) deficiency is an X-linked urea cycle defect. While hemizygous males typically present with hyperammonemic coma in infancy, reports of rare late-onset presentations exist, with poor outcomes in males up to 58 years old. Relatives with mutations identical to affected patients often remain asymptomatic, and it is likely that environmental and genetic factors influence disease penetrance and expression. Here, we present our investigation of a patient with late-onset presentation, and we emphasize the potential role of environmental and genetic factors on disease expression. The patient was a previously healthy 62-year-old man who developed mental slowing, refractory seizures, and coma over an 8-day period. Interestingly, the patient had recently used home gardening fertilizers and pesticides. Evaluations for drug and alcohol use, infections, and liver disease were negative. Despite aggressive therapy, blood NH3 concentration peaked at 2,050 μM and the patient died from cerebral edema and cerebellar herniation. Analysis of the OTC gene showed a Pro-225-Thr (P225T) change in exon 7, a mutation that has been previously implicated in OTC deficiency. This case illustrates that OTC deficiency can cause acute, severe hyperammonemia in a previously healthy adult and that the P225T mutation can be associated with late-onset OTC deficiency. We speculate that exposure to organic chemicals might have contributed to the onset of symptoms in this patient. This case also emphasizes that persistent hyperammonemia may cause irreversible neurologic damage and that after the diagnosis of hyperammonemia is established in an acutely ill patient, certain diagnostic tests should be performed to differentiate between urea cycle disorders and other causes of hyperammonemic encephalopathy.

Valproic Acid—Induced Hyperammonemia in a Patient With Schizoaffective Disorder

Valproic acid is used in psychiatry as a mood stabilizer and can be very effective in reducing symptoms of agitation. Valproic acid may cause hyperammonemia through carnitine deficiency created by its inhibition of mitochondrial enzymes in the urea cycle. Clinical presentation of hyperammonemia usually involves lethargy and somnolence, which may also be noted with therapeutic serum concentration during valproic acid therapy. The diagnosis of hyperammonemia is often overlooked due to a clinical presentation that may include normal liver enzyme tests and serum valproate levels that are within the therapeutic range. Treatment modalities may include discontinuation of valproic acid therapy, lactulose, naloxone, and hemodialysis. Carnitine supplementation, for both prevention and acute treatment of hyperammonemia, has been anecdotally reported and may be considered. This article illustrates a case of an adult male with schizoaffective disorder who was treated with valproic acid and subsequently developed hyperammonemia, despite therapeutic valproic acid serum levels and normal liver enzyme tests. Possible causes of hyperammonemia and current treatment options will be described, as well as suggestions for monitoring for this adverse event in the clinical setting.

Pharmacology Review: Sodium Phenylacetate and Sodium Benzoate in the Treatment of Neonatal Hyperammonemia

Ammonia is present in all body fluids and exists primarily as ammonium ion at physiologic pH. Hyperammonemia is defined as a blood ammonia concentration greater than about 100 mcmol/L in neonates or 50 mcmol/L in children and adults (precise cut-offs vary, depending on individual laboratory normative ranges). The concentration of ammonia is 10 times higher in tissue than in blood. A 5- to 10-fold increase in blood ammonia concentration usually is toxic to the nervous system. Hyperammonemia in the neonatal period, especially when due to inborn errors of metabolism, can progress rapidly and cause severe neurologic damage or early death. Hyperammonemia can be caused by inborn errors of metabolism as well as by a variety of acquired conditions (Tables 1 and 2). Urgent treatment is required because of the potential for irreversible neurologic sequelae that can, in many cases, be prevented by prompt diagnosis and institution of therapy. | Urea cycle defects | || | Amino acid transporter deficiencies | | Organic acidemias | | Fatty acid oxidation defects | | Pyruvate carboxylase deficiency | | Mitochondrial disorders | | Hyperinsulinism/hyperammonemia syndrome (glutamate dehydrogenase mutations) | | Delta1-pyrroline-5-carboxylate synthase deficiency | Table 1. Inborn Errors of Metabolism Associated With Hyperammonemia | Sampling artifact | || | Cardiovascular | | Perinatal asphyxia | | Liver failure | | Bacterial colonization (urease-positive organisms) | | Iatrogenic | Table 2. Causes of Acquired Hyperammonemia The combination of sodium phenylacetate (NAPA) and sodium benzoate (NABZ) in a 10%/10% solution is an intravenously administered United States Food and Drug Administration (FDA)-approved drug used as adjunctive therapy for …

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.