The male neonate in this case study was admitted to the hospital at 15 hours of age due to respiratory distress for 15 hours and poor response for 3 hours after resuscitation from asphyxia. The neonate was highly unresponsive, with central respiratory failure and seizures. Serum ammonia was elevated (>1 000 μmol/L). Blood tandem mass spectrometry revealed a significant decrease in citrulline. Rapid familial whole genome sequencing revealed OTC gene mutations inherited from the mother. Continuous hemodialysis filtration and other treatments were given. Neurological assessment was performed by cranial magnetic resonance imaging and electroencephalogram. The neonate was diagnosed with ornithine transcarbamylase deficiency combined with brain injury. He died at 6 days of age after withdrawing care. This article focuses on the differential diagnosis of neonatal hyperammonemia and introduces the multidisciplinary management of inborn error of metabolism.
Humans ; Infant, Newborn ; Male ; Citrulline ; Electroencephalography ; Hyperammonemia ; Ornithine Carbamoyltransferase Deficiency Disease/therapy* ; Seizures

Neonatal hyperammonemia is a disorder of ammonia metabolism that occurs in the neonatal period. It is a clinical syndrome characterized by abnormal accumulation of ammonia in the blood and dysfunction of the central nervous system. Due to its low incidence and lack of specificity in clinical manifestations, it is easy to cause misdiagnosis and missed diagnosis. In order to further standardize the diagnosis and treatment of neonatal hyperammonemia, the Youth Commission, Subspecialty Group of Neonatology, Society of Pediatrics, Chinese Medical Association formulated the expert consensus based on clinical evidence in China and overseas and combined with clinical practice experience,and put forward 18 recommendations for the diagnosis and treatment of neonatal hyperaminemia.
Humans ; Infant, Newborn ; Ammonia ; China ; Consensus ; Hyperammonemia/therapy*

OBJECTIVES: To investigate genotype-phenotype characteristics and long-term prognosis of neonatal carbamoyl phosphate synthetase 1 (CPS1) deficiency among children through newborn screening in Zhejiang province. METHODS: The clinical and follow-up data of children with CPS1 deficiency detected through neonatal screening and confirmed by tandem mass spectrometry and genetic testing in Zhejiang Province Newborn Disease Screening Center from September 2013 to August 2023 were retrospectively analyzed. RESULTS: A total of 4 056 755 newborns were screened and 6 cases of CPS1 deficiency were diagnosed through phenotypic and genetic testing. Ten different variations of CPS1 genewere identified in genetic testing, including 2 known pathogenic variations (c.2359C>T and c.1549+1G>T) and 8 unreported variations (c.3405-1G>T, c.2372C>T, c.1436C>T, c.2228T>C, c.2441G>A, c.3031G>A, c.3075T>C and c.390-403del). All patients had decreased citrulline levels (2.72-6.21 μmol/L), and varying degrees of elevated blood ammonia. The patients received restricted natural protein intake (special formula), arginine and supportive therapy after diagnosis, and were followed-up for a period ranging from 9 months to 10 years. Three patients experienced hyperammonemia, and one patient each had attention deficit hyperactivity disorder, transient facial twitching and increased muscle tone. One patient died, while the other five surviving patients had normal scores of the Ages & Stages Questionnaires (ASQ) and Griffiths Development Scales up to the present time; 4 cases had combined height or weight lag and one case was normal in height and weight. CONCLUSIONS Low citrulline levels and hyperammonemia are common in CPS1 deficiency patients in Zhejiang. Most gene variants identified were specific to individual families, and no hotspot mutations were found. Early diagnosis through newborn screening and following standardized treatment can significantly improve the prognosis of the patients.
Child ; Humans ; Infant, Newborn ; Carbamoyl-Phosphate Synthase I Deficiency Disease/therapy* ; Neonatal Screening ; Follow-Up Studies ; Hyperammonemia ; Citrulline/genetics* ; Retrospective Studies ; Mutation

OBJECTIVE: To study the efficacy and safety of continuous renal replacement therapy (CRRT) in the treatment of neonates with inherited metabolic diseases and hyperammonemia. METHODS: A retrospective analysis was performed on the medical records of neonates with inherited metabolic diseases and hyperammonemia who were hospitalized and underwent CRRT in the Department of Neonatology, Hunan Children's Hospital, from September 2016 to March 2020, including general conditions, clinical indices, laboratory markers, and adverse reactions. RESULTS: A total of 11 neonates were enrolled, with 7 boys (64%) and 4 girls (36%). The neonates had a mean gestational age of (38.9±0.8) weeks, a mean body weight of (3 091±266) g on admission, and an age of (5.7±2.0) days at the time of CRRT. The main clinical manifestations were vomiting (100%), convulsions (100%), and coma (55%), and the main primary disease was urea cycle disorder (55%). The mean duration of CRRT was (44±14) hours, the medium duration of coma before CRRT was 2 hours, and the total duration of coma was 10 hours. The patients had a mean hospital stay of (18±10) days and a survival rate of 73%, and 2 survivors had epilepsy. After treatment, all patients had significant reductions in blood ammonia, lactic acid, and K CONCLUSIONS CRRT is safe and effective in the treatment of neonates with inherited metabolic diseases and hyperammonemia.
Acute Kidney Injury ; Child ; Continuous Renal Replacement Therapy ; Female ; Humans ; Hyperammonemia/therapy* ; Infant ; Infant, Newborn ; Length of Stay ; Male ; Metabolic Diseases/therapy* ; Retrospective Studies

Ornithine transcarbamylase deficiency(OTCD)is a most common ornithine cycle (urea cycle) disorder. It is a X-link inherited disorder caused by
Humans ; Hyperammonemia/etiology* ; Liver Transplantation ; Nervous System Diseases/prevention & control* ; Ornithine Carbamoyltransferase Deficiency Disease/therapy*

PURPOSE: Nutritional therapy (NT), such as enteral nutrition (EN) or parenteral nutrition (PN), is essential for the malnourished patients. Although the complications related to NT has been well described, multicenter data on symptoms in the patients with receiving NT during hospitalization are still lacking. METHODS: Nutrition support team (NST) consultations, on which NT-related complications were described, were collected retrospectively for one year. The inclusion criteria were patients who were (1) older than 18 years, (2) hospitalized, and (3) receiving EN or PN at the time of NST consultation. The patients' demographics (age, sex, body mass index [BMI]), type of NT and type of complication were collected. To compare the severity of each complication, the intensive care unit (ICU) admission, hospital stay, and type of discharge were also collected. RESULTS: A total of 14,600 NT-related complications were collected from 13,418 cases from 27 hospitals in Korea. The mean age and BMI were 65.4 years and 21.8 kg/m2. The complications according to the type of NT, calorie deficiency (32.4%, n=1,229) and diarrhea (21.6%, n=820) were most common in EN. Similarly, calorie deficiency (56.8%, n=4,030) and GI problem except for diarrhea (8.6%, n=611) were most common in PN. Regarding the clinical outcomes, 18.7% (n=2,158) finally expired, 58.1% (n=7,027) were admitted to ICU, and the mean hospital days after NT-related complication were 31.3 days. Volume overload (odds ratio [OR]=3.48) and renal abnormality (OR=2.50) were closely associated with hospital death; hyperammonemia (OR=3.09) and renal abnormality (OR=2.77) were associated with ICU admission; “micronutrient and vitamin deficiency” (geometric mean [GM]=2.23) and volume overload (GM=1.61) were associated with a longer hospital stay. CONCLUSION: NT may induce or be associated with several complications, and some of them may seriously affect the patient's outcome. NST personnel in each hospital should be aware of each problem during nutritional support.
Adult ; Body Mass Index ; Demography ; Diarrhea ; Enteral Nutrition ; Hospitalization ; Humans ; Hyperammonemia ; Intensive Care Units ; Korea ; Length of Stay ; Multicenter Studies as Topic ; Nutrition Therapy ; Nutritional Support ; Parenteral Nutrition ; Referral and Consultation ; Retrospective Studies ; Vitamins

Hyperammonemia can be caused by several genetic inborn errors of metabolism including urea cycle defects, organic acidemias, fatty acid oxidation defects, and certain disorders of amino acid metabolism. High levels of ammonia are extremely neurotoxic, leading to astrocyte swelling, brain edema, coma, severe disability, and even death. Thus, emergency treatment for hyperammonemia must be initiated before a precise diagnosis is established. In neonates with hyperammonemia caused by an inborn error of metabolism, a few studies have suggested that peritoneal dialysis, intermittent hemodialysis, and continuous renal replacement therapy (RRT) are effective modalities for decreasing the plasma level of ammonia. In this review, we discuss the current literature related to the use of RRT for treating neonates with hyperammonemia caused by an inborn error of metabolism, including optimal prescriptions, prognosis, and outcomes. We also review the literature on new technologies and instrumentation for RRT in neonates
Ammonia ; Astrocytes ; Brain Edema ; Coma ; Diagnosis ; Edema ; Emergency Treatment ; Humans ; Hyperammonemia ; Infant, Newborn ; Metabolism ; Metabolism, Inborn Errors ; Peritoneal Dialysis ; Plasma ; Prescriptions ; Prognosis ; Renal Dialysis ; Renal Replacement Therapy ; Urea

BACKGROUND/AIMS: L-carnitine not only alleviates hyperammonemia and reduces muscle cramps in patients with liver cirrhosis, but also improves anemia in patients with chronic hepatitis and renal dysfunction. This study prospectively evaluated the preventative efficacy of L-carnitine supplementation against hemolytic anemia during antiviral treatment using ribavirin in patients with hepatitis C virus (HCV)-related chronic liver disease. METHODS: A total of 41 patients with chronic hepatitis were consecutively enrolled in this study. Group A (n=22) received sofosbuvir plus ribavirin for 3 months, whereas group B (n=19) was treated with sofosbuvir, ribavirin, and L-carnitine. Hemoglobin concentration changes, the effects of antiviral treatment, and the health status of patients were analyzed using short form-8 questionnaires. RESULTS: A significantly smaller decrease in hemoglobin concentration was observed in group B compared to group A at every time point. Moreover, the prescribed dose intensity of ribavirin in group B was higher than that of group A, resulting in a higher ratio of sustained virological response (SVR) 24 in group B compared with group A. The physical function of patients in group B was also significantly improved compared to group A at the end of antiviral treatment. CONCLUSIONS: L-carnitine supplementation alleviates ribavirin-induced hemolytic anemia in patients with HCV and helps relieve the physical burden of treatment with ribavirin-containing regimens. These advantages significantly increase the likelihood of achieving SVR.
Anemia ; Anemia, Hemolytic ; Carnitine ; Drug Therapy ; Hepacivirus ; Hepatitis C ; Hepatitis C, Chronic ; Hepatitis ; Hepatitis, Chronic ; Humans ; Hyperammonemia ; Liver Cirrhosis ; Liver Diseases ; Muscle Cramp ; Prospective Studies ; Ribavirin ; Sofosbuvir

Hyperammonemia syndrome (HS) is a comparatively rare but often fatal clinical syndrome characterized by progressive respiratory alkalosis and abrupt mental status alteration associated with markedly elevated plasma ammonium levels. Although the exact mechanism of HS remains unclear, infection with urease producing microbes is proposed as the main etiology of HS recently. A patient with HS after repeated autologous skin transplantation was admitted to Tianjin First Center Hospital in March 2018, presented with fever, coma and epilepsy. The infection of Mycoplasma hominis was confirmed in blood sample by high throughput gene detection. The patient was survived after multimodal management including antimicrobial treatment, aggressive ammonia removal by continuous renal replacement therapy in combination with lactulose, and mechanical ventilation. She was successfully discharged from intensive care unit (ICU) with clear consciousness, normal temperature and smooth breath. In view of the experience of the case treatment, a review of literature was conducted to discuss the epidemiology and clinical characteristics, possible etiologies and mechanisms, and outcomes with emphasis on treatment strategies of HS and to promote more clinicians to recognize this rare disease.
Female ; Humans ; Hyperammonemia/therapy* ; Intensive Care Units ; Review Literature as Topic ; Skin Transplantation/adverse effects* ; Treatment Outcome

Severe hyperammonemia can occur as a result of inherited or acquired liver enzyme defects in the urea cycle, among which ornithine transcarbamylase deficiency (OTCD) is the most common form. We report a very rare case of a 45-year-old Korean male who was admitted to the intensive care unit (ICU) due to severe septic shock with acute respiratory failure caused by Pneumocystis jiroveci pneumonia. During his ICU stay with ventilator care, the patient suffered from marked hyperammonemia (>1,700 µg/dL) with abrupt mental change leading to life-threatening cerebral edema. Despite every effort including continuous renal replacement therapy and use of a molecular adsorbent recirculating system (extracorporeal liver support-albumin dialysis) to lower his serum ammonia level, the patient was not recovered. The lethal hyperammonemia in the patient was later proven to be a manifestation of acquired liver enzyme defect known as OTCD, which is triggered by serious catabolic conditions, such as severe septic shock with acute respiratory failure.
Ammonia ; Brain Edema ; Humans ; Hyperammonemia* ; Intensive Care Units ; Liver ; Male ; Middle Aged ; Ornithine Carbamoyltransferase Deficiency Disease* ; Ornithine Carbamoyltransferase* ; Ornithine* ; Pneumocystis jirovecii ; Pneumonia ; Renal Replacement Therapy ; Respiratory Insufficiency ; Shock, Septic* ; Urea ; Ventilators, Mechanical