RESUMEN
Portal hypertension has cerebral consequences via its causes and complications, namely hepatic encephalopathy (HE), a common and devastating brain disturbance caused by liver insufficiency and portosystemic shunting. The pathogenesis involves hyperammonemia and systemic inflammation. Symptoms are disturbed personality and reduced attention. HE is minimal or grades I to IV (coma). Bouts of HE are episodic and often recurrent. Initial treatment is of events that precipitated the episode and exclusion of nonhepatic causes. Specific anti-HE treatment is lactulose. By recurrence, rifaximin is add-on. Anti-HE treatment is efficacious also for prophylaxis, but emergence of HE marks advanced liver disease and a dismal prognosis.
Asunto(s)
Encefalopatía Hepática , Hipertensión Portal , Lactulosa , Encefalopatía Hepática/etiología , Encefalopatía Hepática/fisiopatología , Humanos , Hipertensión Portal/etiología , Hipertensión Portal/complicaciones , Hipertensión Portal/fisiopatología , Lactulosa/uso terapéutico , Rifaximina/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Hiperamonemia/etiología , Hiperamonemia/complicacionesRESUMEN
BACKGROUND: Primary carnitine deficiency (PCD) denotes low carnitine levels with an autosomal recessive pattern of inheritance. Cardiomyopathy is the most common cardiac symptom in patients with PCD, and early diagnosis can prevent complications. Next-generation sequencing can identify genetic variants attributable to PCD efficiently. OBJECTIVE: We aimed to detect the genetic cause of the early manifestations of hypertrophic cardiomyopathy and metabolic abnormalities in an Iranian family. METHODS: We herein describe an 8-year-old boy with symptoms of weakness and lethargy diagnosed with PCD through clinical evaluations, lab tests, echocardiography, and cardiac magnetic resonance imaging. The candidate variant was confirmed through whole-exome sequencing, polymerase chain reaction, and direct Sanger sequencing. The binding efficacy of normal and mutant protein-ligand complexes were evaluated via structural modeling and docking studies. RESULTS: Clinical evaluations, echocardiography, and cardiac magnetic resonance imaging findings revealed hypertrophic cardiomyopathy as a clinical presentation of PCD. Whole-exome sequencing identified a new homozygous variant, SLC22A5 (NM_003060.4), c.821G > A: p.Trp274Ter, associated with carnitine transport. Docking analysis highlighted the impact of the variant on carnitine transport, further indicating its potential role in PCD development. CONCLUSIONS: The c.821G > A: p.Trp274Ter variant in SLC22A5 potentially acted as a pathogenic factor by reducing the binding affinity of organic carnitine transporter type 2 proteins for carnitine. So, the c.821G > A variant may be associated with carnitine deficiency, metabolic abnormalities, and cardiomyopathic characteristics.
Asunto(s)
Cardiomiopatías , Cardiomiopatía Hipertrófica , Hiperamonemia , Enfermedades Musculares , Masculino , Humanos , Niño , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/genética , Carnitina/genética , Carnitina/metabolismo , Irán , Miembro 5 de la Familia 22 de Transportadores de Solutos/genética , Hiperamonemia/diagnóstico , Hiperamonemia/genética , Hiperamonemia/complicaciones , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/genética , Cardiomiopatía Hipertrófica/complicaciones , MutaciónRESUMEN
ABSTRACT: Hyperammonemia is a serious clinical condition associated with significant morbidity and mortality. In the pediatric population, this is often caused by urea cycle disorders, acute liver failure, or other less common underlying etiologies. Children and teens with hyperammonemia can have a broad range of clinical findings, including vomiting, respiratory distress, and changes in mental status. As ammonia levels worsen, this presentation can progress to respiratory failure, encephalopathy, cerebral edema, seizures, and death. Given the risk of neurologic damage, timely identification and management of hyperammonemia is critical and includes initial resuscitation, early consultation with subspecialists, and initiation of appropriate therapies. It is important for pediatric emergency medicine providers to understand the clinical findings, causes, diagnosis, and management of hyperammonemia because they play a key role in the provision of effective, multidisciplinary care of these patients.
Asunto(s)
Encefalopatías , Hiperamonemia , Trastornos Innatos del Ciclo de la Urea , Adolescente , Humanos , Niño , Hiperamonemia/complicaciones , Hiperamonemia/diagnóstico , Trastornos Innatos del Ciclo de la Urea/terapia , Encefalopatías/complicaciones , Convulsiones , Servicio de Urgencia en HospitalRESUMEN
OBJECTIVE: Treatment of bipolar disorder (BD) involves complexities especially when patients come with significant sensitivity to various psychotropic medications and comorbidities. The following cases aim to recapitulate and discuss some of such situations. CASES: Case 1: A 36-year-old man with intellectual development disorder and BD experienced catatonia, seizures, and hyperammonemia following valproate administration. Treatment involved electroconvulsive therapy (ECT) and a tailored medication regimen, ultimately leading to stability. Case 2: A 63-year-old man with long-standing BD exhibited resistance to lithium and valproate of late, having co-existing essential tremors and cerebellar atrophy. Multiple medication trials led to side effects, requiring ECT for symptom improvement, followed by a carefully adjusted maintenance regimen. CONCLUSION: Medication side effects can pose major challenges in treatment of BD. Comprehensive evaluation and monitoring are essential. ECT can prove valuable in such cases. There is pressing need to develop more safer treatment alternatives, especially considering the progressively ageing society.
Asunto(s)
Antipsicóticos , Trastorno Bipolar , Hiperamonemia , Masculino , Humanos , Adulto , Persona de Mediana Edad , Trastorno Bipolar/diagnóstico , Ácido Valproico/efectos adversos , Antipsicóticos/uso terapéutico , Hiperamonemia/inducido químicamente , Hiperamonemia/terapia , Hiperamonemia/complicaciones , Atrofia/inducido químicamente , Atrofia/complicaciones , Atrofia/tratamiento farmacológicoRESUMEN
PURPOSE: Acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) patients have high short-term mortality and morbidity. In the context of liver failure, increased serum ammonia is associated with worse neurological outcomes, including high-grade hepatic encephalopathy (HE), cerebral edema, and intracranial hypertension. Besides its neurotoxicity, hyperammonemia may contribute to immune dysfunction and the risk of infection, a frequent trigger for multi-organ failure in these patients. MATERIAL AND METHODS: We performed a literature-based narrative review. Publications available in PubMed® up to June 2023 were considered. RESULTS: In the ICU management of liver failure patients, serum ammonia may play an important role. Accordingly, in this review, we focus on recent insights about ammonia metabolism, serum ammonia measurement strategies, hyperammonemia prognostic value, and ammonia-targeted therapeutic strategies. CONCLUSIONS: Serum ammonia may have prognostic value in liver failure. Effective ammonia targeted therapeutic strategies are available, such as laxatives, rifaximin, L-ornithine-l-aspartate, and continuous renal replacement therapy.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Edema Encefálico , Encefalopatía Hepática , Hiperamonemia , Humanos , Amoníaco , Hiperamonemia/complicaciones , Insuficiencia Hepática Crónica Agudizada/terapiaRESUMEN
BACKGROUND & AIMS: Dysbiosis contributes to alcohol-associated liver disease (ALD); however, the precise mechanisms remain elusive. Given the critical role of the gut microbiota in ammonia production, we herein aim to investigate whether and how gut-derived ammonia contributes to ALD. METHODS: Blood samples were collected from human subjects with/without alcohol drinking. Mice were exposed to the Lieber-DeCarli isocaloric control or ethanol-containing diets with and without rifaximin (a nonabsorbable antibiotic clinically used for lowering gut ammonia production) supplementation for five weeks. Both in vitro (NH4Cl exposure of AML12 hepatocytes) and in vivo (urease administration for 5 days in mice) hyperammonemia models were employed. RNA sequencing and fecal amplicon sequencing were performed. Ammonia and triglyceride concentrations were measured. The gene and protein expression of enzymes involved in multiple pathways were measured. RESULTS: Chronic alcohol consumption causes hyperammonemia in both mice and human subjects. In healthy livers and hepatocytes, ammonia exposure upregulates the expression of urea cycle genes, elevates hepatic de novo lipogenesis (DNL), and increases fat accumulation. Intriguingly, ammonia promotes ethanol catabolism and acetyl-CoA formation, which, together with ammonia, synergistically facilitates intracellular fat accumulation in hepatocytes. Mechanistic investigations uncovered that ATF4 activation, as a result of ER stress induction and general control nonderepressible 2 activation, plays a central role in ammonia-provoked DNL elevation. Rifaximin ameliorates ALD pathologies in mice, concomitant with blunted hepatic ER stress induction, ATF4 activation, and DNL activation. CONCLUSIONS: An overproduction of ammonia by gut microbiota, synergistically interacting with ethanol, is a significant contributor to ALD pathologies.
Asunto(s)
Amoníaco , Hígado Graso , Hiperamonemia , Hepatopatías Alcohólicas , Animales , Humanos , Ratones , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo , Amoníaco/efectos adversos , Amoníaco/metabolismo , Etanol/efectos adversos , Etanol/metabolismo , Hígado Graso/inducido químicamente , Hígado Graso/metabolismo , Hiperamonemia/complicaciones , Hiperamonemia/metabolismo , Hiperamonemia/patología , Lipogénesis , Hígado/metabolismo , Hepatopatías Alcohólicas/metabolismo , Ratones Endogámicos C57BL , Rifaximina/farmacologíaRESUMEN
Hyperammonemia is characterized by the excessive accumulation of ammonia in the body as a result of the loss of liver detoxification, leading to the development of hepatic encephalopathy (HE). These metabolic alterations carry cognitive and motor deficits and cause neuronal damage, with no effective treatment at present. In this study, we aimed to evaluate the effect of two subacute oral administrations of flaxseed oil (0.26 and 0.52 mL/kg) on short- and long-term memory, visuospatial memory, locomotor activity, motor coordination, and the neuronal morphology of the prefrontal cortex (PFC) via tests on Wistar rats with hyperammonemia. The goal was to identify its role in the regulation of cerebral edema, without liver damage causing cerebral failure. In contrast with an ammonium-rich diet, flaxseed oil and normal foods did not cause cognitive impairment or motor alterations, as evidenced in the short-term and visuospatial memory tests. Furthermore, the flaxseed oil treatment maintained a regular neuronal morphology of the prefrontal cortex, which represents a neuroprotective effect. We conclude that the oral administration of flaxseed oil prevents cognitive and motor impairments as well as neuronal alterations in rats with hyperammonemia, which supports the potential use of this oil to ameliorate the changes that occur in hepatic encephalopathy.
Asunto(s)
Lino , Encefalopatía Hepática , Hiperamonemia , Ratas , Animales , Encefalopatía Hepática/etiología , Encefalopatía Hepática/prevención & control , Encefalopatía Hepática/metabolismo , Ratas Wistar , Aceite de Linaza/farmacología , Hiperamonemia/complicaciones , CogniciónRESUMEN
OBJECTIVES: To determine whether hyperammonemia has a direct impact on steatohepatitis in mice fed with a high-fat diet (HFD). METHODS: Male C57BL/6 mice were divided into two groups receiving either chow diet or HFD. After 12-week NASH modeling, hyperammonemia was induced by intragastric administration of ammonium chloride solution (NH4 Cl) or liver-specific carbamoyl phosphate synthetase 1 (Cps1) knockdown. In vitro experiments were performed in HepG2 cells induced by free fatty acid (FFA) and NH4 Cl. RESULTS: NH4 Cl administration led to increased levels of plasma and hepatic ammonia in NASH mice. NH4 Cl-induced hyperammonemia did not influence liver histological changes in mice fed with HFD; however, elevated plasma cholesterol level, and an increasing trend of liver lipid content were observed. No significant effect of hyperammonemia on hepatic inflammation and fibrosis in NASH mice was found. In vitro cell experiments showed that NH4 Cl treatment failed to increase the lipid droplet content and the expressions of de novo lipogenesis genes in HepG2 cells induced by FFA. The knockdown of Cps1 in HFD-fed mice resulted in elevated plasma ammonia levels but did not cause histological change in the liver. CONCLUSIONS: Our study revealed a limited role of ammonia in aggravating the progression of NASH. Further studies are needed to clarify the role and mechanism of ammonia in NASH development.
Asunto(s)
Hiperamonemia , Enfermedad del Hígado Graso no Alcohólico , Masculino , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Hiperamonemia/complicaciones , Hiperamonemia/metabolismo , Amoníaco/metabolismo , Ratones Endogámicos C57BL , Hígado/patología , Dieta Alta en Grasa/efectos adversos , Modelos Animales de EnfermedadRESUMEN
Hepatic encephalopathy (HE) is a neuropsychiatric hepaticinduced syndrome in which several factors are involved in promoting brain perturbations, with ammonia being the primary factor. Motor impairment, incoordination, and gut dysbiosis are some of the wellknown symptoms of HE. Nevertheless, the link between the direct effect of hyperammonemia and associated gut dysbiosis in the pathogenesis of HE is not well established. Thus, this work aimed to assess motor function in hyperammonemia and gut dysbiosis in mice. Twentyeight Swiss mice were distributed into three groups: twoweek and fourweek hyperammonemia groups were fed with an ammoniarich diet (20% w/w), and the control group was pairfed with a standard diet. Motor performance in the three groups was measured through a battery of motor tests, namely the rotarod, parallel bars, beam walk, and static bars. Microbial analysis was then carried out on the intestine of the studied mice. The result showed motor impairments in both hyperammonemia groups. Qualitative and quantitative microbiological analysis revealed decreased bacterial load, diversity, and ratios of both aerobic and facultative anaerobic bacteria, following two and four weeks of ammonia supplementation. Moreover, the Shannon diversity index revealed a timedependent cutback of gut bacterial diversity in a treatmenttimedependent manner, with the presence of only Enterobacteriaceae, Streptococcaceae, and Enterococcaceaeat at four weeks. The data showed that ammoniainduced motor coordination deficits may develop through direct and indirect pathways acting on the gutbrain axis.
Asunto(s)
Microbioma Gastrointestinal , Encefalopatía Hepática , Hiperamonemia , Ratones , Animales , Encefalopatía Hepática/complicaciones , Encefalopatía Hepática/metabolismo , Eje Cerebro-Intestino , Disbiosis/complicaciones , Hiperamonemia/complicaciones , Hiperamonemia/metabolismo , Amoníaco/toxicidadRESUMEN
l-Ornithine (Orn) is a core amino acid responsible for ammonia detoxification in the body via the hepatic urea cycle. Clinical studies in Orn therapy have focused on interventions for hyperammonemia-associated diseases, such as hepatic encephalopathy (HE), a life-threatening neurological symptom affecting more than 80% of patients with liver cirrhosis. However, its low molecular weight (LMW) causes Orn to diffuse nonspecifically and be rapidly eliminated from the body after oral administration, resulting in unfavorable therapeutic efficacy. Hence, Orn is constantly supplied by intravenous infusion in many clinical settings; however, this treatment inevitably decreases patient compliance and limits its application in long-term management. To improve the performance of Orn, we designed self-assembling polyOrn-based nanoparticles for oral administration through ring-opening polymerization of Orn-N-carboxy anhydride initiated with amino-ended poly(ethylene glycol), followed by acylation of free amino groups in the main chain of the polyOrn segment. The obtained amphiphilic block copolymers, poly(ethylene glycol)-block-polyOrn(acyl) (PEG-block-POrn(acyl)), enabled the formation of stable nanoparticles (NanoOrn(acyl)) in aqueous media. We employed the isobutyryl (iBu) group for acyl derivatization in this study (NanoOrn(iBu)). In the healthy mice, daily oral administration of NanoOrn(iBu) for one week did not induce any abnormalities. In the mice exhibiting acetaminophen (APAP)-induced acute liver injury, oral pretreatment with NanoOrn(iBu) effectively reduced systemic ammonia and transaminases levels compared to the LMW Orn and untreated groups. The results suggest that the application of NanoOrn(iBu) is of significant clinical value with the feasibility of oral delivery and improvement in APAP-induced hepatic pathogenesis. STATEMENT OF SIGNIFICANCE: Liver injury is often accompanied by hyperammonemia, a life-threatening condition characterized by elevated blood ammonia levels. Current clinical treatments for reducing ammonia typically entail the invasive approach of intravenous infusion, involving the administration of l-ornithine (Orn) or a combination of Orn and L-aspartate. This method is employed due to the poor pharmacokinetics associated with these compounds. In our pursuit of enhancing therapy, we have developed an orally administrable nanomedicine based on Orn-based self-assembling nanoparticle (NanoOrn(iBu)), which provides sustained Orn supply to the injured liver. Oral administration of NanoOrn(iBu) to healthy mice did not cause any toxic effects. In a mouse model of acetaminophen-induced acute liver injury, oral administration of NanoOrn(iBu) surpassed Orn in reducing systemic ammonia levels and liver damage, thereby establishing NanoOrn(iBu) as a safe and effective therapeutic option.
Asunto(s)
Hiperamonemia , Ratones , Animales , Hiperamonemia/inducido químicamente , Hiperamonemia/complicaciones , Hiperamonemia/tratamiento farmacológico , Ornitina/farmacología , Ornitina/uso terapéutico , Ornitina/metabolismo , Acetaminofén/farmacología , Polímeros/farmacología , Amoníaco/metabolismo , Amoníaco/farmacología , Nanomedicina , Hígado , Polietilenglicoles/farmacologíaRESUMEN
SLC25A13 gene mutations are responsible for diseases related to citrin deficiency (CD), such as neonatal intrahepatic cholestasis caused by citrin deficiency and adult-onset type II citrullinemia (CTLN2). From childhood to adulthood, CD patients are apparently healthy due to metabolic compensation with peculiar dietary habits-disliking high-carbohydrate foods and liking fat and protein-rich foods. Carbohydrate overload and alcohol consumption may trigger the sudden onset of CTLN2, inducing hyperammonemia and consciousness disturbance. Well-compensated asymptomatic CD patients are sometimes diagnosed as having non-obese (lean) non-alcoholic fatty liver disease and steatohepatitis, which have the risk of developing into liver cirrhosis and hepatocellular carcinoma. CD-induced fatty liver demonstrates significant suppression of peroxisome proliferator-activated receptor α and its downstream enzymes/proteins involved in fatty acid transport and oxidation and triglyceride secretion as a very low-density lipoprotein. Nutritional therapy is an essential and important treatment of CD, and medium-chain triglycerides oil and sodium pyruvate are useful for preventing hyperammonemia. We need to avoid the use of glycerol for treating brain edema by hyperammonemia. This review summarizes the clinical and nutritional features of CD-associated fatty liver disease and promising nutritional interventions.
Asunto(s)
Colestasis , Citrulinemia , Hiperamonemia , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Recién Nacido , Niño , Adolescente , Adulto Joven , Citrulinemia/complicaciones , Citrulinemia/terapia , Proteínas de Transporte de Membrana Mitocondrial/genética , Hiperamonemia/complicaciones , Colestasis/complicaciones , Carbohidratos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , MutaciónRESUMEN
A 91-year-old woman was brought to our hospital with altered consciousness. Blood tests showed an increased ammonia level of 468 µg/dL and a normal liver function. Chest computed tomography showed massive right pleural effusion with loculation. We immediately performed chest drainage using two drainage tubes. The pleural effusate pH was 8.5. We diagnosed her with right empyema leading to hyperammonemia and initiated ampicillin/sulbactam therapy. However, she developed progressive renal failure and died on the third day. Empyema caused by urease-producing bacteria can lead to hyperammonemia. This is the first report of hyperammonemia due to empyema in the English literature.
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Empiema , Hiperamonemia , Derrame Pleural , Femenino , Humanos , Anciano de 80 o más Años , Hiperamonemia/complicaciones , Hiperamonemia/diagnóstico , Empiema/complicaciones , Empiema/diagnóstico , Derrame Pleural/diagnóstico por imagen , Derrame Pleural/etiología , Derrame Pleural/terapia , Tomografía Computarizada por Rayos X/efectos adversos , Drenaje/métodosRESUMEN
Chronic hyperammonemia is a main contributor to the cognitive and motor impairment in patients with hepatic encephalopathy. Sustained hyperammonemia induces the TNFα expression in Purkinje neurons, mediated by NF-κB activation. The aims were the following: (1) to assess if enhanced TrkB activation by BDNF is responsible for enhanced NF-κB activation in Purkinje neurons in hyperammonemic rats, (2) to assess if this is associated with increased content of NF-κB modulated proteins such as TNFα, HMGB1, or glutaminase I, (3) to assess if these changes are due to enhanced activation of the TNFR1-S1PR2-CCR2-BDNF-TrkB pathway, (4) to analyze if increased activation of NF-κB is mediated by the PI3K-AKT pathway. It is shown that, in the cerebellum of hyperammonemic rats, increased BDNF levels enhance TrkB activation in Purkinje neurons leading to activation of PI3K, which enhances phosphorylation of AKT and of IκB, leading to increased nuclear translocation of NF-κB which enhances TNFα, HMGB1, and glutaminase I content. To assess if the changes are due to enhanced activation of the TNFR1-S1PR2-CCR2 pathway, we blocked TNFR1 with R7050, S1PR2 with JTE-013, and CCR2 with RS504393. These changes are reversed by blocking TrkB, PI3K, or the TNFR1-SP1PR2-CCL2-CCR2-BDNF-TrkB pathway at any step. In hyperammonemic rats, increased levels of BDNF enhance TrkB activation in Purkinje neurons, leading to activation of the PI3K-AKT-IκB-NF-κB pathway which increased the content of glutaminase I, HMGB1, and TNFα. Enhanced activation of this TrkB-PI3K-AKT-NF-κB pathway would contribute to impairing the function of Purkinje neurons and motor function in hyperammonemic rats and likely in cirrhotic patients with minimal or clinical hepatic encephalopathy.
Asunto(s)
Proteína HMGB1 , Encefalopatía Hepática , Hiperamonemia , Ratas , Animales , FN-kappa B/metabolismo , Células de Purkinje/metabolismo , Microglía/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteína HMGB1/metabolismo , Hiperamonemia/complicaciones , Hiperamonemia/metabolismo , Glutaminasa/metabolismo , Encefalopatía Hepática/complicaciones , Encefalopatía Hepática/metabolismoRESUMEN
Nonhepatic hyperammonemia syndrome is a rare cause of neurologic dysfunction and cerebral edema and has most commonly been reported in posttransplant patients. Only recently has opportunistic infection with Ureaplasma species and Mycoplasma hominis been found to be key to the pathogenesis. We describe the cases of 3 immunosuppressed patients who developed hyperammonemia syndrome with new-onset refractory status epilepticus and diffuse cerebral edema. PCR was positive for M hominis in 1 patient and Ureaplasma parvum in the other 2. Despite early diagnostic suspicion and aggressive management with empirical antibiotics, seizure control, hypertonic saline, and ammonia elimination, none of our patients survived this life-threatening infection. Nonhepatic hyperammonemia and new-onset seizures can be presenting features of disseminated Ureaplasma species and M hominis infections in posttransplant patients. Immunosuppression in the absence of organ transplantation is likely sufficient to trigger this entity, as was the case in our third patient. When suspected, empiric combination antibiotics should be used due to high likelihood of resistance. The diagnostic test of choice is PCR. Patients with hyperammonemia syndrome associated with these infections typically have a poor prognosis. Early recognition and aggressive multimodal interventions may be key to ameliorating the high mortality and severe neurologic sequelae from this entity.
Asunto(s)
Edema Encefálico , Hiperamonemia , Mycoplasma , Estado Epiléptico , Humanos , Ureaplasma , Edema Encefálico/terapia , Edema Encefálico/complicaciones , Hiperamonemia/complicaciones , Hiperamonemia/terapia , Antibacterianos/uso terapéutico , Estado Epiléptico/terapia , Estado Epiléptico/complicacionesRESUMEN
BACKGROUND: Citrullinemia type I (CTLN1) is a rare urea cycle disorder (UCD) with few adult cases described so far. Diagnosis of late-onset CTLN1 is difficult, and delayed treatment may increase the risk of severe hyperammonemia. Pregnancy is an important risk factor for women with CTLN1. However, the clinical manifestations of CTLN1 in a pregnant woman may be mistaken for pregnancy side effects and ultimately delay a timely diagnosis. CASE PRESENTATION: A 34-year-old woman developed vomiting and disturbance of consciousness after 12 weeks of gestation. A blood test showed hyperammonemia (454 µg/dL) with normal liver function tests. She fell into a deep coma, and her serum ammonia level increased to 800 µg/dL. Continuous renal replacement therapy (CRRT) was administered as a diagnostic treatment for UCD and serum ammonia. This patient's case was complicated by co-infection; her dependents decided to withdraw life support and the patient died. She was diagnosed with CTLN1 by analyses of plasma amino acids, urinary orotic acid, and second-generation gene sequencing. DISCUSSION AND CONCLUSION: When a patient displays symptoms of emesis and disturbance of consciousness in early pregnancy, blood ammonia should be monitored, and UCD should be considered, particularly for patients with hyperammonemia in the absence of severe liver function abnormalities.