Recurrent Altered Mental State Associated with Nonhepatic Hyperammonemia Presented in an Elderly Female Patient: Probable Late-Onset Urea Cycle Disorder

Altered mentality associated with hyperammonemia is usually diagnosed in patients with liver disease. Nonhepatic hyperammonemia may be present in critically ill patients or may be caused by high protein diets or certain drugs. Urea cycle disorders (UCDs) rarely present with altered mentality with hyperammonemia in adult patients. An 82-year-old female visited our hospital with complaints of abnormal behavior and confusion. Routine blood tests revealed elevated serum ammonia. Her mentality and serum ammonia level normalized after lactulose enema and she was discharged thereafter. However, she was later re-admitted because of recurrent altered mentality. Amino acid analysis revealed that serum levels of ornithine and glutamine increased significantly, whereas the levels of alanine and glutamic acid increased slightly, and the levels of arginine, lysine, and citrulline were normal, which were probably caused by reduced activity of the mitochondrial ornithine carrier-1. Although our patient was not diagnosed genetically, this case illustrates the under-recognized fact that UCD can occur in a senile age. Clinical suspicion of UCDs in patients with hyperammonemia is critical for early diagnosis and to prevent the significant neurologic sequelae.

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Late-Onset Ornithine Carbamoyltransferase Deficiency Accompanying Acute Pancreatitis and Hyperammonemia

Case Reports in Medicine ◽

10.1155/2013/903546 ◽

2013 ◽

Vol 2013 ◽

pp. 1-3 ◽

Cited By ~ 5

Author(s):

Marcel Cerqueira Cesar Machado ◽

Gilton Marques Fonseca ◽

José Jukemura

Keyword(s):

Urea Cycle ◽

Late Onset ◽

Neuronal Damage ◽

Clinical Care ◽

Subsequent Treatment ◽

Neurological Symptoms ◽

Urea Cycle Disorders ◽

Cycle Disorders ◽

Serum Ammonia ◽

Timely Treatment

Hyperammonemia related to urea cycle disorders is a rare cause of potentially fatal encephalopathy that is encountered in intensive care units (ICUs). Left undiagnosed, this condition may manifest irreversible neuronal damage. However, timely diagnosis and treatment initiation can be facilitated simply by increased awareness of the ICU staff. Here, we describe a patient with acute severe pancreatitis who developed hyperammonemia and encephalopathy without liver disease. Urea cycle disorder was suspected and hemodialysis was initiated. Following reduction of ammonia levels, subsequent treatment included protein restriction and administration of arginine and sodium benzoate. The patient was discharged to home after 47 days with plasma ammonia within normal range and without neurological symptoms. In clinical care settings, patients with neurological symptoms unexplained by the present illness should be assessed for serum ammonia levels to disclose any urea cycle disorders to initiate timely treatment and improve outcome.

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Elevated serum receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in late-onset male hypogonadism

Clinical & Investigative Medicine ◽

10.25011/cim.v34i4.15365 ◽

2011 ◽

Vol 34 (4) ◽

pp. 232 ◽

Cited By ~ 6

Author(s):

Carmen E Pepene ◽

Nicolae Crişan ◽

Ioan Coman

Keyword(s):

Nuclear Factor Kappa B ◽

Late Onset ◽

Elevated Serum ◽

Serum Levels ◽

Sex Hormone Binding Globulin ◽

Male Hypogonadism ◽

Nuclear Factor ◽

Nuclear Factor Kappa ◽

Receptor Activator ◽

Late Onset Hypogonadism

Purpose: Studies that analyze the levels of osteoprotegerin (OPG) or receptor activator of nuclear factor kappa B ligand (RANKL) in hypogonadal men, the majority of whom have prostate cancer or are undergoing androgen-deprivation therapy, are few and inconclusive. Methods: 81 men aged 69.3 ± 0.8 years (39 men with late-onset hypogonadism and 42 age-matched controls) were recruited. Serum levels of OPG, total soluble RANKL (sRANKL), total and free testosterone (FT), estradiol (E2), sex hormone-binding globulin (SHBG), follicle-stimulating hormone, luteinizing hormone (LH), prolactin, bone-specific alkaline phosphatase (BAP) and β-Cross Laps were assessed. Results: Compared with controls, both OPG (p = 0.023) and sRANKL (p = 0.010) serum levels were increased in men with late-onset hypogonadism; however, when expressed as a ratio, sRANKL/OPG, the two groups were not significantly different. Simple and age-adjusted analyses showed that OPG was inversely related to FT and positively related to SHBG, E2 and BAP. In the patient population, LH demonstrated statistically significant correlations with both OPG (r = 0.274, p = 0.013) and sRANKL (r = 0.276, p = 0.018). Multiple regression analysis retained age, SHBG, E2 and BAP as independent predictors of OPG, explaining 27.71% of serum OPG variability. Conclusions: Late-onset hypogonadism is associated with enhanced RANKL activity. Increased bone turnover-related OPG levels may act as a coupling factor between bone resorption and formation. The results suggest anti-RANKL-agents as therapeutic tools in osteoporotic men with late-onset hypogonadism.

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#8: Microbiome and immune disruption accompany mouse death in a gnotobiotic mouse model of neonatal sepsis

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piab031.010 ◽

2021 ◽

Vol 10 (Supplement_2) ◽

pp. S6-S7

Author(s):

D Schwartz ◽

K Wardenburg ◽

N Shalon ◽

J Ning ◽

T Crofts ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Mouse Model ◽

Gut Microbiota ◽

Antibiotic Treatment ◽

Late Onset ◽

Elevated Serum ◽

Serum Levels ◽

Mouse Serum ◽

Gut Permeability

Abstract Background Premature infants frequently receive antibiotics, which diminishes gut microbial diversity and increases susceptibility to infections by antibiotic resistant pathogens. Neonates with decreased gut microbiota diversity, termed dysbiotic, have dysregulated immune systems marked by increased concentrations of circulating activated T cells and decreased concentrations of circulating neutrophils and dendritic cells. We hypothesize that antibiotics (1) enrich for pathogens within the gut, 2) promote a systemic, proinflammatory host response, and 3) cause death in an antibiotic- and microbiome-specific manner in a gnotobiotic model of preterm gut microbiota disruption. Methods We colonized germ free (GF) dams with stools from preterm infants. Mouse pups acquire this neonatal microbiota, and at 10 days of life (DOL), we treat them with clinically-relevant doses of antibiotics subcutaneously for 3 days. We determined serum concentrations of antibiotics in 10 DOL pups using tandem mass spectrometry to achieve approximate pharmacokinetics as observed in the neonatal intensive care unit (NICU). We ascertained phylogenetic composition using metagenomic shotgun sequencing of individual pup fecal samples longitudinally. We performed flow cytometry on peripheral blood and gut permeability assays to determine the local and peripheral immune response. Results We found adding probenecid prolonged the half-life of ampicillin and meropenem allowing for an approximation of serum levels observed in the NICU with an every 8 hour dosing regimen. Using two representative microbiomes from human neonates (hereafter referred to as microbiota A or B), we show that 95% of pups given microbiota A survive versus 54% given microbiota B after meropenem/probenecid treatment (Fig. 1A; p<0.01; n= 18–42 mice in 3–6 independent experiments). Conversely, only 28% of microbiota-A humanized pups survive during ampicillin/probenecid treatment (Fig. 1; p<0.0001). Ampicillin-resistant Klebsiella species and E. coli dominated the gut of microbiota A-humanized pups who succumbed during ampicillin/probenecid treatment whereas Enterococci dominated the gut of microbiota B-humanized pups who died during treatment. To test the reproducibility of this phenotype, we colonized mice with 2 additional preterm neonatal microbiomes with similar compositions to microbiota A and B (D and C, respectively). We found that microbiota-C humanized pups were similarly dominated by Enterococcus faecalis resulting in 42% mortality during meropenem/probenecid treatment (Fig. 1). Pups colonized with microbiota B had decreased circulating granulocytes, B cells, and CD8+ T cells at sacrifice after treatment compared to microbiota A-humanized pups. We next assessed gut permeability after antibiotic treatment by measuring 4kDa FITC-Dextran in mouse serum after oral gavage. Microbiota-A humanized pups treated with ampicillin/probenecid and microbiota B-humanized pups treated with meropenem/probenecid had elevated serum levels of FITC-Dextran (p<0.05 relative to vehicle control, one way ANOVA), indicative of increased gut permeability. Conclusions Our model of preterm microbiota perturbation by antibiotics demonstrates increased gut permeability, proinflammatory immune response, and death dependent on the microbiota-antibiotic combination. Our transgenerational humanized-microbiota mouse model can be utilized to determine antibiotic by microbiota perturbation and examine risks of late onset sepsis from specific antimicrobial administration. This research can lead to a personalized medicine approach of antibiotic treatment in the NICU to limit antibiotic side effects and mortality.

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Type B hepatic encephalopathy due to a congenital superior mesenteric-caval shunt: clinical scenario and therapeutic approach

MedPharmRes ◽

10.32895/ump.mpr.4.4.2 ◽

2020 ◽

Vol 4 (4) ◽

pp. 10-14

Author(s):

Hoang Huu Bui ◽

Van Huy Vo ◽

Viet Khac Doan Tran ◽

Viet Quoc Dang ◽

Long Duy Cong Tran ◽

...

Keyword(s):

Portal Hypertension ◽

Hepatic Encephalopathy ◽

Neuropsychiatric Symptoms ◽

Elevated Serum ◽

Rare Condition ◽

Ammonia Level ◽

Type B ◽

Serum Ammonia Level ◽

Computed Topography ◽

Serum Ammonia

Type B Hepatic encephalopathy (HE) due to a congenital extra-hepatic porto-systemic shunt is an extremely rare condition. We report the case of a 57-year-old woman, with recurrent episodes of confusion and neuropsychiatric symptoms, who had an elevated serum ammonia level and a superior mesenteric-caval shunt documented on abdominal computed topography (CT) scan. There was no evidence of cirrhosis or portal hypertension. A diagnosis of non-cirrhotic, non-portal hypertension hepatic encephalopathy was made after excluding other causes of confusion and cognitive impairment. The patient was successfully treated by radiologically guided endovascular shunt closure and during 9 months follow up, her neuropsychiatric symptoms did not recur and repeated serum ammonia level results were normal.

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Optimal Prescriptions of Continuous Renal Replacement Therapy in Neonates with Hyperammonemia

Blood Purification ◽

10.1159/000492660 ◽

2018 ◽

Vol 47 (1-3) ◽

pp. 16-22 ◽

Cited By ~ 2

Author(s):

Jeong Yeon Kim ◽

Yeonhee Lee ◽

Heeyeon Cho

Keyword(s):

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Therapeutic Option ◽

Ammonia Level ◽

Ultrafiltration Rate ◽

Neurologic Sequelae ◽

Serum Ammonia Level ◽

Poor Outcomes ◽

Serum Ammonia

Background/Aims: The aim of this study was to evaluate patients’ outcomes, determine the prescriptions of continuous renal replacement therapy (CRRT) that effectively reduce serum ammonia levels, and analyze the prognostic factors in neonates with hyperammonemia. Methods: The medical records of 12 Korean neonates with inborn error of metabolism (IEM) who underwent CRRT for hyperammonemia were retrospectively analyzed. Results: All patients received continuous venovenous hemodiafiltration. The median ultrafiltration rate (UFR) at the initiation of CRRT was 2,288.4 mL/h/1.73 m2. The median ammonia level at CRRT initiation was 1,320 µmol/L, and the median time to reduce the initial ammonia level by at least 50% was 12.8 h. The survival rate during hospitalization was 83.3%. There were significant differences between patients with neurologic sequelae and those without poor outcomes in peak serum ammonia level before CRRT and serum ammonia level at CRRT initiation. Conclusion: This study suggested that CRRT could be a therapeutic option for neonates with IEM. However, it is necessary to raise the UFR above 4,000 mL/h/1.73 m2 in patients with high initial ammonia level.

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The Application of Neurodiagnostic Studies to Inform the Acute Management of a Newborn Presenting With Carbamoyl Phosphate Synthetase 1 Deficiency

Child Neurology Open ◽

10.1177/2329048x20985179 ◽

2021 ◽

Vol 8 ◽

pp. 2329048X2098517

Author(s):

Meaghan McGowan ◽

Carlos Ferreira ◽

Matthew Whitehead ◽

Sudeepta K. Basu ◽

Taeun Chang ◽

...

Keyword(s):

Urea Cycle ◽

Response To Treatment ◽

Carbamoyl Phosphate Synthetase ◽

Resonance Imaging ◽

Carbamoyl Phosphate ◽

Neonatal Onset ◽

Neurologic Sequelae ◽

Carbamoyl Phosphate Synthetase 1 ◽

Cycle Disorders ◽

Guide Care

Neonatal-onset urea cycle disorders (UCDs) may result in hyperammonemic (HA) encephalopathy presenting with several neurologic sequelae including seizures, coma, and death. However, no recommendations are given in how and when neurodiagnostic studies should be used to screen or assess for these neurologic complications. We present a case of carbamoyl phosphate synthetase 1 (CPS1) deficiency in a newborn female in which electroencephalogram monitoring to assess encephalopathy and seizures, and magnetic resonance imaging measurements of brain metabolites were used to guide care during her hyperammonemic crisis. Her neurologic course and response to treatment characterizes the significant neurologic impact of HA encephalopathy. Our group herein proposes a clinical neurodiagnostic pathway for managing acute HA encephalopathy.

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Hepatic Encephalopathy

10.1093/med/9780190226459.003.0075 ◽

2017 ◽

Author(s):

Bret Alvis ◽

Amy Robertson

Keyword(s):

Hepatic Encephalopathy ◽

Elevated Serum ◽

Hepatic Function ◽

Ammonia Level ◽

Definitive Treatment ◽

Deep Coma ◽

Anesthetic Considerations ◽

Serum Ammonia Level ◽

Serum Ammonia ◽

Rule Out

Hepatic encephalopathy is a complication of both acute and chronic liver failure. The disease can range from mild cognitive deficits to deep coma. Ammonia accumulation and inflammation are the two most accepted causes of hepatic encephalopathy. It is important to confirm an elevated serum ammonia level and rule out alternative causes of neurological derangements. Nonabsorbable disaccharides are the mainstay of treatment; however, the only definitive treatment is liver transplantation. Pertinent anesthetic considerations include avoiding benzodiazepines, understanding the implications of diminished hepatic function, and recognizing factors that may contribute to increased intracranial cerebral pressure. Proper assessment and management of the patient presenting with hepatic encephalopathy will be discussed.

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Urea Cycle Defects: Early-Onset Disease Associated with A208T Mutation in OTC Gene—Expanding the Clinical Phenotype

Case Reports in Genetics ◽

10.1155/2017/1048717 ◽

2017 ◽

Vol 2017 ◽

pp. 1-3

Author(s):

Ana Isabel Sánchez ◽

Alejandra Rincón ◽

Mary García ◽

Fernando Suárez-Obando

Keyword(s):

Urea Cycle ◽

Late Onset ◽

Clinical Phenotype ◽

High Plasma ◽

Ammonium Concentration ◽

Adult Males ◽

Expanded Newborn Screening ◽

History Of ◽

Otc Deficiency ◽

Cycle Disorders

Ornithine transcarbamylase deficiency (OMIM: 311250) is the most common disorder of urea cycle disorders, accounting for nearly 50% of all cases. We report a case of a two-month- old male patient, who attends our medical genetics consultation because of low citrulline levels and elevated glutamine to citrulline ratio detected by expanded newborn screening with tandem mass spectrometry. He is an asymptomatic male with a normal physical examination and appropriate neurodevelopmental milestones. The patient has a family history of one older brother who died at 18 months old from severe and sudden hyperammonemia and a maternal aunt who suddenly died at two years old. He had high plasma ammonium concentration and a confirmed OTC mutation (p.A208T). Usually, this mutation causes OTC deficiency of late onset in adult males. However, this report raises awareness about mutations previously described as a late-onset causing disease, which can cause severe hyperammonemia and high risk of dying at an early age.

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Hyperammonemia: What Urea-lly Need to Know: Case Report of Severe Noncirrhotic Hyperammonemic Encephalopathy and Review of the Literature

Case Reports in Medicine ◽

10.1155/2016/8512721 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 16

Author(s):

Ruby Upadhyay ◽

Thomas P. Bleck ◽

Katharina M. Busl

Keyword(s):

Case Report ◽

English Language ◽

Clinical Presentation ◽

Urea Cycle ◽

Late Onset ◽

Unique Case ◽

Hyperammonemic Encephalopathy ◽

Search Terms ◽

Otc Deficiency ◽

Cycle Disorders

Purpose. A 66-year-old man who presented with coma was found to have isolated severe hyperammonemia and diagnosed with a late-onset urea-cycle disorder. He was treated successfully and had full recovery.Methods. We report a novel case of noncirrhotic hyperammonemia and review the literature on this topic. Selected literature for review included English-language articles concerning hyperammonemia using the search terms “hyperammonemic encephalopathy”, “non-cirrhotic encephalopathy”, “hepatic encephalopathy”, “urea-cycle disorders”, “ornithine transcarbamylase (OTC) deficiency”, and “fulminant hepatic failure”.Results. A unique case of isolated hyperammonemia diagnosed as late-onset OTC deficiency is presented. Existing evidence about hyperammonemia is organized to address pathophysiology, clinical presentation, diagnosis, and treatment. The case report is discussed in context of the reviewed literature.Conclusion. Late-onset OTC deficiency presenting with severe hyperammonemic encephalopathy and extensive imaging correlate can be fully reversible if recognized promptly and treated aggressively.

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