Hyperammonemic Encephalopathy Research Articles

In-house multiplex ligation-dependent probe amplification assay for citrin deficiency: analytical validation and novel exonic deletions in SLC25A13.

Citrin deficiency is one of the most common inborn errors of metabolism in East Asians, which may manifest as neonatal cholestasis, failure to thrive and dyslipidaemia, or recurrent hyperammonaemic encephalopathy. Its molecular diagnosis requires confirmation of the presence of biallelic pathogenic variants in SLC25A13 gene by sequencing, and analysis for a common insertion IVS16ins3kb. However, patients with compatible biochemical features but only one monoallelic pathogenic variant have remained a diagnostic challenge. Here we report the development, validation and application of a multiplex ligation-dependent probe amplification (MLPA) assay using an in-house oligonucleotide probemix and a customised Coffalyer.NET worksheet for detection of exonic copy number variations in SLC25A13. With this MLPA assay, we successfully identified the presence of a heterozygous exonic deletion in SLC25A13 in three of 15 (20%) unrelated individuals with only one monoallelic pathogenic variant detected using conventional methods. Three exonic deletions, two novel involving exon 14 and one reported involving exon 5, were subsequently confirmed with Sanger sequencing. In summary, we developed, evaluated, and demonstrated the clinical utility of an in-house MLPA assay to look for exonic deletions in SLC25A13 in patients with citrin deficiency. With the discovery of novel deletions, MLPA should be considered a test of choice for molecular diagnosis of citrin deficiency when the sequencing result is inconclusive.

Recurrent noncirrhotic hyperammonemia causing acute metabolic encephalopathy in a patient with a continent ileocecal pouch: a case report

IntroductionAcute encephalopathy, while a common presentation in the emergency department, is typically caused by a variety of metabolic, vascular, infectious, structural, or psychiatric etiologies. Among metabolic causes, hyperammonemia is relatively common and typically occurs in the setting of cirrhosis or liver dysfunction. However, noncirrhotic hyperammonemia is a rare occurrence and poses unique challenges for clinicians.Case presentationHere we report a rare case of a 50-year-old Caucasian female with history of bladder cancer status post chemotherapy, radical cystectomy, and ileocecal diversion who presented to the emergency department with severe altered mental status, combativeness, and a 3-day history of decreased urine output. Her laboratory tests were notable for hyperammonemia up to 289 μmol/L, hypokalemia, and hyperchloremic nonanion gap metabolic acidosis; her liver function tests were normal. Urine cultures were positive for Enterococcus faecium. Computed tomography imaging showed an intact ileoceal urinary diversion with chronic ileolithiasis. Upon administration of appropriate antibiotics, lactulose, and potassium citrate, she experienced rapid resolution of her encephalopathy and a significant reduction in hyperammonemia. Her hyperchloremic metabolic acidosis persisted, but her hypokalemia had resolved.ConclusionThis case is an example of one of the unique consequences of urinary diversions. Urothelial tissue is typically impermeable to urinary solutes. However, when bowel segments are used, abnormal absorption of solutes occurs, including exchange of urinary chloride for serum bicarbonate, leading to a persistent hyperchloremic nonanion gap metabolic acidosis. In addition, overproduction of ammonia from urea-producing organisms can lead to abnormal absorption into the blood and subsequent oversaturation of hepatic metabolic capacity with consequent hyperammonemic encephalopathy. Although this is a rare case, prompt identification and treatment of these metabolic abnormalities is critical to prevent severe central nervous system complications such as altered mental status, coma, and even death in patients with urinary diversions.

Computational extraction and analysis of de-identified medical records to characterize hyperammonemia in patients with fibrolamellar carcinoma (FLC).

e16169 Background: Rare cancers including FLC make up 25% of adult tumors, but are difficult to study due to low incidence and incomplete case identification. FLC occurs in adolescents and young adults without liver dysfunction. Hyperammonemia has been frequently reported in FLC patients, but is poorly understood. Methods: Data from three clinical trials allowed us to establish the incidence of hyperammonemia (serum ammonia value > 75 µmol/L) in FLC. In these studies, FLC patients received everolimus, estrogen deprivation therapy (EDT) with leuprolide + letrozole or everolimus + EDT (Oncologist. 2020 25(11):925-e1603), ENMD-2076 (Oncologist. 2020 25(12):e1837-e1845), or neratinib (J Clin Oncol 39, 2021 (suppl 3; abstr 310); ammonia was tested prospectively in the latter two studies. To assess impacts of cancer therapy or liver dysfunction, we studied hyperammonemia in FLC and non-FLC patients at UCSF in parallel. Using Natural Language Processing (NLP) of pathology reports and oncology notes from > 2300 liver cancer patients from the last 12 years of UCSF records, we identified a cohort of patients with FLC, contrasting their laboratory data to all UCSF patients with ammonia testing for the last 10 years. We used leiden clustering and umap dimensionality reduction to contrast FLC and other patients to assess the clinical context of hyperammonemia. Results: Data from the 3 trials showed hyperammonemia in 10 of 32 (31.3%) FLC patients during study participation, independent of the therapy received. These patients exhibited hyperammonemia with varying levels, and at different points in their treatment. NLP identified 37 patients with FLC ( < 0.1% of liver cancer patients), with 33% showing hyperammonemia. Across all UCSF patients, we found 24,000 independent visits where ammonia was tested, with > 2400 demonstrating hyperammonemia. Using leidan clustering on all encounters with ammonia > 75 µmol/L, we found distinct subsets of hyperammonemia corresponding to known metabolic and physiologic processes (e.g., fulminant liver failure, tumor lysis syndrome, etc). FLC patients clustered separately from hepatocellular carcinoma patients with hyperammonemic encephalopathy due to cirrhosis. Conclusions: NLP of large EMRs is a valuable tool to study FLC, a rare cancer. Herein, we have defined hyperammonemia as a frequent event in FLC, not directly linked to hepatic dysfunction or individual therapies. Further investigation may determine whether hyperammonemia is related to FLC tumor biology.

Hyperammonemia in Patients With Status Epilepticus Treated With or Without Valproic Acid.

Hyperammonemia is a common side effect of valproic acid (VPA) and can occur after generalized seizures, but the clinical significance is unclear. The aim of this study was to better understand the clinical practice and utility of ammonia testing in status epilepticus (SE) treated with or without VPA. Charts of adult patients with SE from St. Mary's Hospital Intensive Care Units (ICUs) (Mayo Clinic, Rochester, MN) from 2011 to 2016 were reviewed. Clinical factors were compared between patients who had ammonia checked versus those who did not, and those with normal ammonia versus hyperammonemia (>50 µg/dL). Charts were reviewed to determine if hyperammonemia changed clinical management and if it was felt to be symptomatic. There were 304 patients identified: 94 received VPA, 142 had ammonia checked and receiving VPA was associated with ammonia testing (P<0.001). Hyperammonemia was identified in 32 and associated with younger age, being in a non-neurological intensive care unit, and liver disease, but was not statistically associated with VPA. Only one patient had valproate-induced hyperammonemic encephalopathy; however, many patients received treatment for hyperammonemia such as lactulose, levocarnitine, or VPA dose reductions. This study demonstrated variability in ammonia testing and management changes in SE but does not support the routine monitoring of ammonia levels and showed that hyperammonemic encephalopathy was rare in this clinical setting.

Acute hyperammonemic encephalopathy – an indication for an extracorporeal depuration technique A case report and literature review

Introduction: Ammonia is a resultant molecule from the protein metabolism that can be neurotoxic when present in high concentrations, causing brain edema and encephalopathy. Extracorporeal blood purification technique (EBPT) can play a role in reducing both ammonia and urea blood levels. However, there are no specific guidelines for its use in hyperammonemia, due to its low incidence and scarce literature on this subject, particularly in adults. Case report: The authors describe a case of a 22 -year -old previously healthy woman. She presented with polyuria, polydipsia, anorexia, vomiting and significant (&gt;10%) weight loss over a month. Laboratory data revealed hypoglycemia and a high anion gap metabolic acidosis with severe acidemia with normal lactate, serum creatinine of 1.12 mg/dl and 260 (reference value 26 -74) umol/l of ammonia. Urine analysis showed ketone bodies. She evolved with progressive encephalopathy and neurological deterioration. The hypothesis of hyperammonemic encephalopathy secondary to a hereditary metabolic disease was suspected. Medical supportive therapy was initiated. An EBPT for ammonia removal and acid -base correction was initiated using continuous venovenous hemodiafiltration (CVVHDF) with a drastic neurologic improvement. A fatty acid beta -oxidation deficit was discovered. The patient was discharged with no neurological changes, with a strict diet free of fat, animal protein and high -protein vegetables, plus supplementation with benzoate, carnitine, riboflavin, maltodextrine and essential amino acids. Discussion and conclusion: In adults, hyperammonemia related to metabolic disorders is rare, and in the presence of encephalopathy, ECDT should be considered. Ammonia is easily dialysable either by intermittent or continuous techniques. CVVHDF provides a continuous clearance with less rebound effect.

Acute Plasma Cell Leukemia Presenting as Primary Hyperammonemic Encephalopathy

Primary plasma cell leukemia (PPCL) is a rare form of multiple myeloma (MM) and is a rare aggressive disease with a median overall survival of 6 - 11 months. We present a case of acute hyperammonemic encephalopathy as the initial presentation of PPCL in a 78-year-old woman to highlight an atypical presentation of this disorder. J Med Cases. 2020;11(10):320-323 doi: https://doi.org/10.14740/jmc3559

Acute Hypoxic Respiratory Failure /Hyperammonemic encephalopathy in the setting of concurrent use of valproic acid and topiramate

Valproic acid (VPA) is widely used for the treatment of epilepsy, migraine, and a variety of psychiatric symptoms, including bipolar disorder, borderline personality disorder, and alcohol withdrawal. Valproate is associated with severe idiosyncratic adverse effects, the most notable being valproate-induced hyperammonemic encephalopathy (VHE). Topiramate is also a broad-spectrum anticonvulsant that is also extensively used for migraine prophylaxis, as a mood stabilizer, and for alcohol dependency. There is increased occurrence of VHE when valproate is used with other medications like phenytoin, phenobarbital, and topiramate. We report a young patient who was on valproic acid and topiramate and developed metabolic encephalopathy with hypoxic respiratory failure with review of the causes and management of the hyperammonemic encephalopathy. We believe that clinicians should be aware of possible hyperammonemic encephalopathy in any patient who is taking valproic acid and presenting with impaired consciousness and cognitive decline. We also underline the importance of early recognition and high index of suspicion of encephalopathy related to hyperammonemia.

Transient Hyperammonemic Encephalopathy in a Child with Relapsed Acute Lymphoblastic Leukemia and Severe Tumor Lysis Syndrome

AbstractIdiopathic hyperammonemia (IHA) is a severe condition, which has been reported in intensive chemotherapy and bone marrow transplantation. This case elucidates the diagnostic dilemma in children undergoing initiation of chemotherapy and developing severe disorders of qualitative and quantitative consciousness in the presence of hyperammonemia (HA) and lactic acidosis. The role of mitoxantrone as a causative agent for IHA in children is elusive. Children undergoing chemotherapy are often in a poor general condition, and the clinical presentation of HA is heterogeneous. This case should be a reminder for clinicians to check for HA in children with tumor lysis syndrome and acute neurological deterioration.

Starting stiripentol in adults with Dravet syndrome? Watch for ammonia and carnitine.

Dravet syndrome (DS) is a rare cause of severe and pharmacoresistant epileptic encephalopathy. Stiripentol (STP) has a significant therapeutic benefit in the pediatric DS population. However, STP effects on adult patients have not been well studied. In our adult STP-naive DS patient population, STP initiation was associated with encephalopathy, despite decreases in valproate and clobazam dosage. Here we explored the cause and treatment of encephalopathic manifestations associated with STP in adults. Twenty-eight patients with a confirmed clinical and genetic diagnosis of DS who attended the Adult Epilepsy Genetics Clinic were identified retrospectively. Patients who declined or discontinued STP after fewer than 3months of use, patients who were deceased before starting STP or seizure-free when the genetic diagnosis was confirmed, and those who started STP before leaving the pediatric system (<18years) were excluded. Levels of ammonia, carnitine, and other anti-epileptic drugs (AEDs) were observed for patients receiving STP. Patients with high ammonia levels who received carnitine supplementation were reevaluated. They were also offered an increased dosage of stiripentol if treatment with carnitine improved the encephalopathy. We observed hyperammonemic encephalopathy in 77% of patients treated with STP. In seven of nine patients, we observed a rate of improvement in ammonia levels of 35% (95% confidence interval [CI] 21%-49%) at a mean carnitine dose of 991±286mg/d (range 660-1320mg/d). Five patients whose ammonia levels normalized were also offered an increase in STP dose and they were able to tolerate higher doses with improvement in side effects. Despite such adjustments, the mean maximum stiripentol dose reached was 14.89±8.72mg/kg/d, which is lower than what is typically recommended in children (50mg/kg/d). We report hyperammonemia in adult STP-naive patients who were on valproate and clobazam, despite dose reduction of the latter drugs. We also report that treatment with carnitine improved hyperammonemia, allowing the continuation of STP.

Primary hyperammonaemia: Current diagnostic and therapeutic strategies.

Primary hyperammonaemia is a term to describe an elevation of ammonia in blood or plasma due to a defect within the urea cycle, which is the pathway responsible for ammonia detoxification and arginine biosynthesis. Urea cycle disorders (UCDs) are rare diseases caused by genetic defects affecting any of the six enzymes or two transporters that are directly involved in the urea cycle function.The clinical situation is variable and largely depends on the time of onset. Newborns who are often affected by hyper-ammonaemic encephalopathy carry a potential risk of severe brain damage, which may lead to death. Outside the neonatal period, symptoms are very unspecific but most often neurological (with wide variability), psychiatric and/or gastrointestinal. Early identification of patients is extremely important to start effective treatment modalities immediately. The acute management includes detoxification of ammonia, which often requires extracorporeal means such as haemodialysis, and the use of intravenous drugs that work as nitrogen scavengers. Long-term management of patients with UCDs consists of a low-protein diet, which needs to be balanced and supplemented to avoid deficiencies of essential amino acids, trace elements or vitamins and the use of nitrogen scavengers.The reader will find here a brief overview describing the most relevant aspects of the clinical management of UCDs in an attempt to raise awareness for this important group of rare diseases.

BYPASSING THE UREA CYCLE IN THE ICU

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Hyperammonemic encephalopathy is a rare, yet devastating complication of Rou-en-Y gastric bypass surgery. Though the mechanisms which underlie this complication are not completely understood, a partial underlying inborn error of metabolism has been proposed. In this case we describe a patient who presented with worsening altered mental status and ultimately improved after empiric treatment for a partial urea cycle disorder. CASE PRESENTATION: A 45 year-old female with a history of Roux-en-Y gastric bypass and recently diagnosed bilateral pulmonary emboli presented with altered mental status. One day prior to admission, she became lethargic and ultimately unresponsive, prompting her family to bring her to the hospital. She had 60 lbs of weight loss in the last 2 months, which her family attributed to poor oral intake. In the last 6 months, she had multiple episodes of dizziness, falls, and syncope as well as multiple admissions for nausea, intractable vomiting, and abdominal pain. On presentation, the patient was hemodynamically stable.Abdominal ultrasound revealed changes consistent with steatosis without evidence of cirrhosis. Laboratory results were significant for elevated ammonia (169 µmol/L) and INR (1.7). The patient was started on lactulose and rifaximin for suspected hepatic encephalopathy. After three days of therapy, the patient’s mental status declined and ammonia levels had increased to 192 µmol/L. She was intubated and started on continuous renal replacement therapy (CRRT) for ammonia clearance. Mental status improved. However, cessation of CRRT resulted in increased ammonia levels and worsening mental status. Further laboratory studies revealed deficiencies in zinc, selenium, and copper. Given the refractory hyperammonemia, encephalopathy, and history of gastric bypass surgery, the patient was started on treatment for a suspected partial urea cycle disorder, including arginine and sodium benzoate, as well as supplementation of zinc and copper, resulting in improvement of ammonia levels and mental status. Ultimately, the patient was discharged to an outside facility. DISCUSSION: Encephalopathy in the ICU patient is a frequent occurrence, and may be due to a myriad of metabolic derangements. Inborn errors of metabolism are not common in adult ICU patients, but should be considered in those with a history of gastric bypass surgery presenting with refractory hyperammonemia. As seen in our case, this deadly complication may be reversible with prompt initiation of empiric treatment. CONCLUSIONS: A rare complication of Rou-en Y gastric bypass surgery, hyperammonemic encephalopathy should be considered in patients with refractory hyperammonemia and a history of gastric bypass surgery. Reference #1: Fenves, A.Z., Shchelochkov, O.A. and Mehta, A. (2015), Hyperammonemic syndrome after Roux-en-Y gastric bypass. Obesity, 23: 746-749. doi:10.1002/oby.21037 Reference #2: Nagarur, A., & Fenves, A. Z. (2017). Late Presentation of Fatal Hyperammonemic Encephalopathy After Roux-En-Y Gastric Bypass. Baylor University Medical Center Proceedings, 30(1), 41–43. doi: 10.1080/08998280.2017.11929521 DISCLOSURES: No relevant relationships by Abigail Go, source=Web Response No relevant relationships by John Mwangi, source=Web Response No relevant relationships by Ara Vartanyan, source=Web Response

Stiripentol: risk of hyperammonaemic encephalopathy

Stiripentol: risk of hyperammonaemic encephalopathy

Incidence, Presentation, and Risk Factors for Sodium Valproate–Associated Hyperammonemia in Neurosurgical Patients: A Prospective, Observational Study

Sodium valproate (VPA) is a commonly prescribed antiepileptic drug (AED) in daily neurosurgical practice. However, the incidence of VPA-associated hyperammonemia (VAH) and its life-threatening consequence, VPA-induced hyperammonemic encephalopathy (VHE), in neurosurgical patients is unknown. We determined the incidence, clinical presentation, and risk factors for VAH. This prospective cohort study was performed on adult neurosurgical patients prescribed VPA for at least a week over a 22-month period. Blood tests for ammonia, VPA, and liver function were performed at the time of recruitment. The primary end point was VAH. Secondary end points were VHE and liver dysfunction. In total, 252 patients were recruited. The commonest disease etiology was brain tumors (27%, 69), followed by aneurysmal subarachnoid hemorrhage (SAH; 26%, 65). VPA was prescribed for primary seizure prophylaxis in 110 patients (44%). The mean daily dose was 1148 mg for a mean duration of 48 months. The mean serum VPA level was 417 μmol/L. In total, 92 patients (37%) were prescribed an additional AED, the most common being phenytoin (65%, 60/92). The mean serum ammonia level was 47 μmol/L. In total, 28% (71/252) of patients had VAH and only 0.7% had VHE. Independent factors were aneurysmal SAH (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.1-4.2), concomitant phenytoin (aOR 1.9; 95% CI 1.0-3.5), and phenobarbital (aOR 4.6; 95% CI 1.1-20.0). No associations with VPA dose, duration, serum levels, and liver function were observed. Although VAH is common among neurosurgical patients, VHE is rare. Patients with aneurysmal SAH or on concomitant enzyme-inducing AEDs are at risk. Clinicians should be vigilant for VHE symptoms in these patients.

Abstract 4353: The Fibrolamellar Registry: A patient-based medical registry can address medical care

Abstract Advances in genomics and proteomics have enabled more precise characterizations of tumors with the consequence that many cancers are being segregated into smaller categories. With this larger number of categories, more cancers are being categorized as rare. The downside to such categorizations is that the reduced numbers of patients in each category makes it difficult to gather enough information about each cancer. We are a group of patients and caregivers who have joined together to form a repository for patient-shared data and reports in an IRB-approved, non-profit medical registry for the rare and usually lethal childhood liver cancer fibrolamellar hepatocellular carcinoma (FLC). Since the Fibrolamellar Registry is patient-run and patient-owned, we have the trust of the patient community that the records will not be sold for profit. This has enabled us, in our first 3 years, to gather detailed medical records, scans and tests from over 170 patients. With input from scientists and clinicians who study FLC, we have written 600 questions of specific interest to this disease. Most of our patients have also opted to allow these medical records to be shared with a tissue FLC repository that already has samples from 110 patients. Many of patients with FLC get hyperammonenic encephalopathy. These patients do not respond to lactulose and, unfortunately, often enter a coma and die from the condition. From evaluation of our medical records the results indicate that patients do not have hyperammonenic encephalopathy as a result of liver failure. Instead, it is the result of an alteration of the expression of ornithine transcarbamylase, as a consequence of the expression of oncokinase that drives fibrolamellar. These alterations of ornithine transcarbamylase shift the urea acid cycle, resulting in the buildup of ammonia. This suggests that hyperammonemic encephalopathy should be treated with agents that modulate the urea acid cycle rather than lactulose. These results are an example of the power of a patient-run medical registry. Citation Format: Julie Latone Newcomb, Siobhan Lett, Rachael D. Migler, Elana P. Simon, Sanford M. Simon. The Fibrolamellar Registry: A patient-based medical registry can address medical care [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4353.

Hyperammonemic encephalopathy as a manifestation of Reye syndrome in a previously-healthy 14-year-old girl: a case report

Hyperammonemic encephalopathy as a manifestation of Reye syndrome in a previously-healthy 14-year-old girl: a case report

Pancreatic Neuroendocrine Tumor-Induced Hyperammonemic Encephalopathy in the Absence of Hepatic Involvement.

Pancreatic Neuroendocrine Tumor-Induced Hyperammonemic Encephalopathy in the Absence of Hepatic Involvement.

An Effective Way to Treat Hyperammonemic Encephalopathy Complicated Post-Distal Roux-en-Y Gastric Bypass Surgery.

An Effective Way to Treat Hyperammonemic Encephalopathy Complicated Post-Distal Roux-en-Y Gastric Bypass Surgery.

Diabetes mellitus exacerbates citrin deficiency via glucose toxicity

AimsCitrin is an aspartate/glutamate carrier that composes the malate-aspartate reduced nicotinamide adenine dinucleotide (NADH) shuttle in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), failure to thrive and dyslipidemia (FTTDCD) and adult–onset type II citrullinemia (CTLN2). Hepatic glycolysis is essentially impaired in citrin deficiency and a low-carbohydrate diet was recommended. The lethal effect of infusion of glycerol- and fructose-containing osmotic agents was reported in these patients. Hyperalimentation was also reported to exacerbate CTLN2; however, glucose toxicity was unclear in citrin deficiency. MethodsWe studied two CTLN2 patients complicated with type 2 diabetes mellitus (DM), Case 1 presented with hyperammonemic encephalopathy accompanied with DM, while Case 2 presented with hyperammonemic encephalopathy relapse upon the onset of DM after several years’ remission following supplementation with medium-chain triglycerides (MCT) and adherence to a low-carbohydrate diet. ResultsInsulin therapy with MCT supplementation and a low-carbohydrate diet improved hyperammonemia and liver function in Case 1. Additional insulin therapy improved hyperammonemia in Case 2. ConclusionGlucose is not toxic for citrin deficiency in normoglycemia because glucose uptake and metabolism by hepatocytes are limited in normoglycemia. However, glucose becomes toxic during persistent hyperglycemia and antidiabetic therapy is indispensable for CTLN2 patients with DM.

Ammonia and coma \u2013 a case report of late onset hemizygous ornithine carbamyltransferase deficiency in 68-year-old female

BackgroundAcute hyperammonemia without signs of common causes in the elderly might be challenging to identify. We report the oldest case known to date of a female patient with late onset ornithine carbamyltransferase deficiency (OTC), which was unmasked after a protein overload due to nutritional supplements. Our case illustrates how environmental factors (protein overload) in previously unknown OTC in the elderly leads to hyperammonemic encephalopathy and highlights that early treatment prevents persisting neurological deficits and should be considered in absence of common causes of hyperammonemic encephalopathy.Case presentationA 68-year-old woman presented with acute confusion, which progressed into a deep coma (Glasgow-Coma-Scale score 3) within a few hours.The only remarkable finding was a plasma ammonia (NH3) concentration of 697 μmmol/l (range 12–47 μmmol/). Third party history revealed that the patient disliked meat for most of her life (meat = protein, which needs to be metabolized) and had taken nutritional supplements (since supplements often have a high protein-ratio) 2 days before the symptoms started. Protein catabolism results in NH3, which is metabolized via the urea cycle. Consequently, the acute hyperammonemia in our patient was thought to be related to an inherited metabolic disorder, which only unmasked itself as a result of an overload of the corresponding metabolite (in this case protein). Since ornithine carbamyltransferase deficiency (OTC) is the most common inherited urea cycle disorder, this diagnosis became likely and was confirmed later via genetic and metabolic testing (amino acids, orotic acid, etc.). After 2 weeks of treatment (dialysis, low-protein-diet, nitrogen-lowering medication) the patient was discharged in a healthy condition without any neurological deficits.ConclusionOTC is a x-chromosomal linked disorder, that usually manifests in newborn infants and children, but also rarely in adults and even rarer in the elderly (50- till 60-years-old), where it is probably underdiagnosed. In case of hyperammonemic encephalopathy – regardless of the underlying cause -, treatment should be started early to prevent persisting neurological deficits. OTC should be considered in absence of common causes of hyperammonemic encephalopathy.

VALPROATE-INDUCED HYPERAMMONEMIC ENCEPHALOPATHY IN A CHILD WITHOUT HEPATIC FAILURE: A CASE REPORT

Sodium valproate or valproic acid (VPA) is an effective antiepileptic drug that is commonly used for epilepsy in children because of its broad-spectrum activity. The use of VPA frequently results in elevated plasma levels of ammonia with or without raised transaminases. This condition usually happens when VPA with polypharmacy or underlying metabolic disorders like urea cycle defects. We are reporting a case of valproate-induced hyperammonemic encephalopathy in a child which is rare in children. Health professionals should be aware of this potential complication, and it is highly recommended to check ammonia levels in patients taking VPA who present with a change in mental status. If identified early, it can treat with appropriate measures and it can reversible.