Clinical findings of patients with hyperammonemia affected by urea cycle disorders with hepatic encephalopathy

Abstract

Urea cycle disorders (UCD) are a group of genetic diseases caused by deficiencies in the enzymes and transporters involved in the urea cycle. The impairment of the cycle results in ammonia accumulation, leading to neurological dysfunctions and poor outcomes to affected patients. The aim of this study is to investigate and describe UCD patients' principal clinical and biochemical presentations to support professionals on urgent diagnosis and quick management, aiming better outcomes for patients. We explored medical records of 30 patients diagnosed in a referral center from Brazil to delineate UCD clinical and biochemical profile. Patients demonstrated a range of signs and symptoms, such as altered levels of consciousness, acute encephalopathy, seizures, progressive loss of appetite, vomiting, coma, and respiratory distress, in most cases combined with high levels of ammonia, which is an immediate biomarker, leading to a UCD suspicion. The most prevalent UCD detected were ornithine transcarbamylase deficiency, followed by citrullinemia type 1, hyperargininemia, carbamoyl phosphate synthase 1 deficiency, and argininosuccinic aciduria. Clinical symptoms were highly severe, being the majority developmental and neurological disabilities, with 20% of death rate. Laboratory analysis revealed high levels of ammonia (mean AE SD: 860 AE 470 μmol/L; reference value: ≤80 μmol/L), hypoglycemia, metabolic acidosis, and high excretion of orotic acid in the urine (except in carbamoyl phosphate synthetase 1 [CPS1] deficiency). We emphasize the need of urgent identification of UCD clinical and biochemical conditions, and immediate measurement of ammonia, to

Could the Urease of the Gut Bacterium Proteus mirabilis Play a Role in the Altered Gut–Brain Talk Associated with Parkinson’s Disease?

“…Although not measured here, hyperammonemia could be expected in mice treated with the enzymatically active PMU. However, if present, the ammonia levels probably are only mildly increased, as no motor symptoms characteristic of hyperammonemia, such as ataxia, altered levels of consciousness, seizures, loss of appetite, vomiting, coma, or respiratory distress, were noticed [ 131 , 132 , 133 ]. In this context, it is worth mentioning that in rats injected with canatoxin or JBU, alterations in synaptic plasticity with persistent long-term depression were observed at a time that the animals showed extreme prostration [ 55 ].…”

Urea cycle disorders in critically Ill adults

“…Mild UCDs should be suspected alongside a suggestive family history or when patients have a longstanding history of neurologic, psychiatric and gastrointestinal symptoms [17]. This "symptom triad" can include broad neurologic complaints including chronic mild encephalopathy, autism, specific learning disorders, seizures, headaches, ataxia or altered muscle tone, and even slurred speech or pseudostroke [1 && , 15,17,18]. Mood or behavioral disorders, delirium, visual hallucinations, psychosis, and nonspecific gastrointestinal complaints also occur [15,17].…”

“…This "symptom triad" can include broad neurologic complaints including chronic mild encephalopathy, autism, specific learning disorders, seizures, headaches, ataxia or altered muscle tone, and even slurred speech or pseudostroke [1 && , 15,17,18]. Mood or behavioral disorders, delirium, visual hallucinations, psychosis, and nonspecific gastrointestinal complaints also occur [15,17]. Since protein intake increases demand on the urea cycle, patients often self-select a vegetarian or low-protein diet.…”

“…Diagnosing a mild UCD hinges upon capturing an elevation in ammonia, but this laboratory evaluation is often omitted from the initial assessment. For critically ill patients without previously diagnosed UCDs or other inborn errors of metabolism (IEMs), screening for hyperammonemia in the setting of a broad grouping of unexplained neurologic symptoms is recommended (Table 1) [1 ▪▪ ,2 ▪ ,11,15]. It is important to note that elevated ammonia levels are sometimes the result of sampling technique, and mild-to-moderate elevations should be rechecked [1 ▪▪ ,2 ▪ ].…”