Search

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2022 American Academy of Neurology.)

We describe a 21-month-old male with relapsed clear cell sarcoma of the kidney receiving enteral nutrition who experienced recurrent, ketotic hypoglycemia. During relapse therapy, he had recurrent hypoglycemia episodes, in the setting of hematochezia and diarrhea. Evaluation revealed low carnitine levels. He received supplementation with oral levocarnitine throughout the remainder of treatment, resulting in normalization of serum carnitine levels and no further hypoglycemia. We believe adverse effects of the chemotherapy on his single kidney and gastrointestinal insult resulted in hypoglycemia and carnitine deficiency. Our case highlights that carnitine deficiency should be considered when acute onset hypoglycemia without obvious cause occurs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Ornithine transcarbamylase deficiency (OTCD) is the most common X-linked hereditary disorder of urea cycle disorders that is caused by neonatal hyperammonemia. OTC gene sequence variations are common causes of OTCD. The current study presents a 28-month-old baby girl proband with phenotypical characteristics of OTCD such as irritability, somnolence, intermittent vomiting, and high levels of serum ammonium. Whole-exome sequencing revealed a de novo c.275G>A p.(Arg92Gln) variant within the OTC gene. In silico analysis revealed a possible differential affinity between wild-type and mutant OTCase, while Arg92Gln decreases the binding ability of OTCase to the substrate, which can disrupt the urea cycle and explains the molecular pathogenicity of clinical hyperammonemia. In light of the fact that the genotype and phenotype correlation of OTCD is still uncertain, the present in silico analysis outcome can enhance our knowledge on this complicated, rare, and severe genetic disorder., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: FOLFOX therapy is the main chemotherapy regimen for colorectal cancer. Peripheral neuropathy, hematotoxicity, and digestive symptoms are known to be the most frequent adverse events. Hyperammonemia and lactic acidosis rarely occur simultaneously during treatment with FOLFOX therapy; the number of case reports is limited worldwide. We report a case of disturbance of consciousness, considered to be caused by hyperammonemia and lactic acidosis that occurred during treatment with mFOLFOX6 therapy that was administered as postoperative adjuvant treatment for rectal cancer., Patient Concerns: This case was of a 71-year-old man who had been receiving oral treatment for chronic kidney disease and diabetes mellitus. Laparoscopic low anterior resection and artificial anal construction surgery were performed for stage III rectal cancer. As adjuvant postoperative therapy, mFOLFOX6 therapy was started but was followed by a disturbance of consciousness., Diagnoses: Results of the blood tests revealed notable hyperammonemia (ammonia level, 1,163 μg/dl) and lactic acidosis (pH 7.207; lactate, 17.56 mmol/L); however, imaging diagnosis did not reveal intracranial lesions that could cause disturbance of consciousness., Interventions: For hyperammonemia, branched-chain amino acid agents and Ringers solution supplementation were administered. For acidosis, 7% sodium hydrogen carbonate was administered as treatment., Outcomes: The disturbance of consciousness improved within 12 hours of initiating the treatment, and the patient was discharged with no sequelae on 7th day after hospitalization., Conclusion: In patients with chronic kidney disease, FOLFOX regimen may confer risks of hyperammonemia and lactic acidosis.

A case of a 19-year-old female with low-risk acute myeloid leukemia is presented who was diagnosed with idiopathic hyperammonemic encephalopathy following the development of abrupt neurologic decline, respiratory alkalosis, and elevated plasma ammonia levels of unknown etiology. Delayed symptom recognition of this exceedingly rare condition contributes to the often fatal outcomes of idiopathic hyperammonemic encephalopathy. As illustrated by this case, prompt diagnosis and utilization of a variety of ammonia-modulating treatment modalities can result in remarkable clinical recovery. This case provides guidance to clinicians in counseling families about the possibility of neurologic recovery in similar clinical scenarios.

Background: Although rare, symptomatic hyperammonemia is sometimes associated with valproic acid (VPA), especially in children. L-carnitine (levocarnitine), sometimes classified as an essential amino acid, is vital to mitochondrial utilization of fatty acids and can be helpful in treating this condition. The data supporting this, however, are limited., Study Question: The aim of the study was to illustrate the role of L-carnitine in the treatment of patients with VPA-induced hyperammonemic encephalopathy (VPE) at 2 different institutions., Methods: Medical records of affected patients were reviewed; data collected included exposure history, clinical manifestations, physical examination, and laboratory values., Results: There were 13 cases of VPE; 12 were associated with therapeutic dosing and 1 with an overdose. The maximum ammonia concentration was 557 μmol/L, and blood concentrations of VPA ranged from 68 to 600 μg/mL (therapeutic range 50-100 μg/mL). In all cases, liver function tests were normal or only mildly increased. In this study, 12 patients received a daily dose of L-carnitine 100 mg/kg, and 1 received 200 mg/kg (intravenous infusion over 30 minutes) divided every 8 hours until clinical improvement. All patients made a full recovery. None developed adverse effects or reactions, and no cases of toxicity were reported., Conclusion: Our series suggests that intravenous L-carnitine, at a dose of 100 mg·kg·d in 3 divided doses each over 30 minutes until clinical improvement occurs, is a safe and effective treatment in the management of VPE in children.

Hepatic encephalopathy is a complication of liver failure characterized by neuropsychiatric dysfunction ranging from disorientation to coma. There is a need for more treatment options and preventive care interventions to reduce the incidence of hepatic encephalopathy and mitigate its socioeconomic impact on families and strain on healthcare resources. Currently, there is no consensus on a single pathophysiological mechanism responsible for the development of this neurocognitive disorder. Ammonia toxicity remains a significant factor, but there is now increased recognition that hyperammonemia acts synergistically with systemic inflammation, oxidative stress, and gut microbiota imbalance in the development of hepatic encephalopathy. This article provides an overview of current and emerging therapies that target these factors in the treatment and management of this condition. Because of its complex pathogenesis, a multipronged approach to treating hepatic encephalopathy may be highly beneficial.

Background: Primary systemic carnitine deficiency (SCD) is an autosomal-recessive disorder caused by SLC22A5 gene mutation resulting in defective cellular carnitine transporter organic cation transporter 2. Defective carnitine transporter causes renal carnitine wasting and low serum carnitine. Carnitine is an essential cofactor for the transportation of long-chain fatty acids into the mitochondria. Lacking of carnitine may cause metabolic decompensation and sudden death when the patient is exposed to prolonged fasting before an operation., Methods: An asymptomatic 9-month-old boy with SCD diagnosed by local hospital was referred to the authors' hospital for incomplete cleft palate plastic surgery. Due to potential metabolic decompensation from prolonged fasting before the surgery, the patient underwent proper perioperative management., Results: The operation was successful and subsequent clinical course was fine. The patient was discharged on postoperative day 3., Conclusion: With proper perioperative management, patients with SCD and cleft palate can survive from prolonged fasting time before and during operation without metabolic decompensation manifestations. Early recognition of SCD and perioperative management can be lifesaving in preoperative infants with SCD.

We describe an infant with concomitant hypercalcemia and hyperammonemia associated with nonanion gap metabolic acidosis secondary to distal renal tubular acidosis (dRTA). The levels of both serum calcium and ammonia rapidly normalized with the correction of dehydration and metabolic acidosis. To the best of our knowledge, there has been only one previous case report of concomitant hypercalcemia and hyperammonemia associated with dRTA that has been reported in the literature. We describe the causes and emergent management of hypercalcemia and review the possible mechanisms of this rare association with dRTA.

Ornithine transcarbamylase deficiency is an inborn error of metabolism that commonly presents as hyperammonemia in neonates. We present a case of a 2-year-old girl who was referred to a pediatric emergency department for evaluation of hepatitis, an uncommon presentation of ornithine transcarbamylase deficiency. Recognition of late presentations of this disease is important for survival and neurological outcome.

We report on two Aboriginal patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Both presented with acute hepatic failure with severe hypertransaminasemia and coagulopathy, prompting evaluation for emergent liver transplantation. The diagnosis of HHH syndrome was based on the presence of typical metabolic abnormalities. A protein-restricted diet and L-arginine or L-citrulline supplementation were immediately started, with rapid normalization of liver function test results and other biochemical abnormalities. Molecular analysis of the SLC25A15 gene showed that the two patients were homozygous for the common French Canadian mutation (F188Delta). The diagnosis of HHH syndrome should be considered in patients with unexplained fulminant hepatic failure. There does not appear to be a genotype-phenotype correlation for this presentation, inasmuch as the only other reported patient presenting with this picture had two different point mutations. Early identification and prompt treatment of these patients is crucial to avoid liver transplantation and can be life saving.

The authors report the clinical and molecular findings in eight patients with hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome. The most consistent neurologic finding was spastic paraparesis, seen in five of the eight patients. However, all showed signs of pyramidal tract involvement. A broad spectrum of pathogenetic mutations (including missense, nonsense, splice site, insertion, and deletions) were identified in the ORNT1 gene.