Consensus on diagnosis and treatment of ornithine trans-carbamylase deficiency / 浙江大学学报·医学版

Ornithine transcarbamylase deficiency(OTCD)is a most common ornithine cycle (urea cycle) disorder. It is a X-link inherited disorder caused by

Uso de Hemofiltración veno-venosa continua en neonatos con hiperamonemia. Serie clínica / Continuous venovenous hemofiltration in neonates with hyperammonemia. A case series

Resumen: Introducción: La hiperamonemia neonatal secundaria a errores congénitos del metabolismo es una entidad poco frecuente pero con una alta tasa de secuelas neurológicas y mortalidad. El manejo médico inicial es en muchas ocasiones insuficiente para detener el progresivo aumento de la amonemia, con el consecuente deterioro del paciente. Por esta razón se han implementado técnicas depurativas entre las que se cuenta la diálisis peritoneal, la hemodiálisis intermitente y las terapias de reemplazo renal continuo (TRRC). Objetivo: Describir nuestra experiencia en diálisis extracorpórea continua en pacientes con hiperamonemia neonatal gravemente enfermos. Pacientes y Método: Revisión retrospectiva de fichas clínicas de neonatos con hiperamonemias secundarias a errores congénitos del metabolismo sometidos a TRRC, admitidos en nuestra institución en los últimos 6 años. Se obtuvieron datos demográficos, edad cronológica y gestacional, género; datos antropométricos y de laboratorio (creatininemia, amonemia) e índice de gravedad por PIM-II. Se analizó la TRRC utilizada: modalidad, duración y complicaciones. El inicio de la terapia dependió de la respuesta al manejo médico en las primeras 24 horas, compromiso neurológico progresivo, o cifras de amonio sanguíneo elevados (> 400 μg/dl) al momento del ingreso. Las TRRC fueron realizadas con la máquina Prisma Flex, usando filtros M100 y/o HF20. Resultados: 6 neonatos, 4 varones, la mitad con antecedentes de prematurez, todos con compromiso neurológico agudo severo y amonemias en rango grave (> 1.000 μg/dl). La edad y peso promedio al iniciar la TRRC fueron de 10 días y 2.798 g respectivamente, amonemia (mediana) 1.663 μg/dl (rango 1.195-3.097). El puntaje PIM-II tuvo una mediana de 53 (rango 13,4-87,4). En promedio, los pacientes estuvieron 49,5 h en la terapia continua. En cuatro neonatos se usó una técnica dialítica mixta convectiva y difusiva (hemodiafiltración), y solo convectiva (hemofiltración) en las 2 restantes. La mortalidad fue de 33%, y uno de los sobrevivientes quedó con daño neurológico moderado permanente en seguimiento clínico. Conclusiones: Los resultados obtenidos en este grupo de neonatos extremadamente graves nos incentivan a proponer esta terapia dialítica como una excelente alternativa en el manejo de este tipo de pacientes.

Abstract: Introduction: Neonatal hyperammonemia secondary due to inborn errors of metabolism is a rare condition with a high rate of neurological sequelae and mortality. Initial medical management is often insufficient to stop the progressive increase of ammonia, with the consequent deterioration of the patient. For this reason, depurative techniques have been implemented, including peritoneal dialysis, intermittent hemodialysis and continuous renal replacement therapy (CRRT). Objective: To describe our experience with continuous extracorporeal dialysis in severely ill neonates with hyperammonemia. Patients and Methods: Retrospective review of clinical records of neonates with hyperammonemia due to congenital errors of metabolism undergoing CRRT admitted in our institution in the last 6 years. Demographic data, chronological and gestational age, gender, anthropometric and laboratory data (creatininemia, ammonemia), and severity index PIM-II where collected. It was analyzed the CRRT: modality, duration and complications. The stard of therapy depended on the response to medical management in the first 24 hours, progressive neurological involvement, or increased blood ammonia (> 400 qg/dl) at the time of admission. CRRTs were performed using the Prisma Flex system and M100 and/or HF20 filters. Results: 6 neonates, 4 males, half of them with a history of prematurity, all with severe acute neurological involvement and severe ammonemias (> 1,000 qg/dl). The average age and weight at the start of the CRRT were 10 days and 2798 g, respectively, ammonia (median) 1,663 qg/dl (range 1,195 - 3,097). The PIM-II score had a median of 53 (range 13.4 - 87.4). On average, patients were 49.5 hours in continuous therapy. In four neonates, a mixed convective and diffusive technique (hemodiafiltration) was used, and only convective one (hemofiltration) in the 2 remaining. Mortality was 33%, and one of the survivors had permanent moderate neurological damage in clinical follow-up. Conclusions: The results obtained in this extremely ill group of neonates encourage us to propose this dialytic therapy as an excellent alternative in the management of this type of patients.

Encefalopatía hiperamoniémica secundaria a infección urinaria por germen productor de ureasa: Caso clínico pediátrico / Hyperammonemic encephalopathy due to urinary tract infection by urea splitting bacteria: A pediatric case report

El incremento del amonio en sangre, hiperamoniemia, es pasible de provocar compromiso neurológico al atravesar la barrera hematoencefálica. La causa más frecuente y conocida de hiperamoniemia es la alteración en la función hepática. Sin embargo, se deben considerar otras patologías, de menor frecuencia y poco conocidas. La infección del tracto urinario por gérmenes productores de ureasa debe ser contemplada a pesar de ser infrecuente en pediatría. Se reporta el caso de un niño con encefalopatía aguda grave, con niveles elevados de amonio en sangre, en quien, luego de descartar otros diagnósticos diferenciales, se asumió el cuadro como hiperamoniemia secundaria a infección del tracto urinario por Corynebacterium riegelii, un germen productor de ureasa. Se implementaron medidas generales de tratamiento para la encefalopatía hiperamoniémica y tratamiento antibiótico específico, con buena evolución el paciente.

Elevated level of ammonia in the blood, defined as hyperammonemia, is feasible to cause neurological symptoms when crossing the blood-brain barrier. The most frequent and studied cause of hyperammonemia is liver failure. Nevertheless, other less frequent and known etiologies must be considered. Urinary tract infection caused by urea-splitting bacteria, despite being unusual in pediatric patients, must be taken into account. We report a pediatric patient with severe acute encephalopathy and high levels of ammonia in blood. After ruling out other causes of hyperammonemia, it was assumed secondary to urinary tract infection by Corynebacterium riegelii, a ureasplitting bacteria. General treatment for hyperammonemic encephalopathy was established, as well as specific treatment with antibiotics. The patient evolved favorably.

Recurrent Hyperammonemia After Abernethy Malformation Type 2 Closure: a Case Report

ABSTRACT The Abernethy malformation is a rare congenital malformation defined by the presence of an extrahepatic portosystemic shunt. Although most patients are asymptomatic, clinical encephalopathy is present in 15% of cases. We present a patient with type 2 Abernethy malformation, hyperammonemia, and encephalopathy. Shunt closure was performed successfully using interventional angiography; however, hyperammonemia recurred 3 months later. The diagnosis of Abernethy malformation can be made easily, but the ideal patient management strategy has not yet been established. This is the first reported patient with recurrence of hyperammonemia after interventional treatment; we discuss the therapeutic options for Abernethy malformation.(AU)

Encefalopatía hiperamoniémica y hepatocarcinoma fibrolamelar / Hyperammonemic encephalopathy and fibrolamellar hepatocellular carcinoma

Presentamos el caso de una mujer de 22 años con hepatocarcinoma fibrolamelar agresivo, metastásico, de rápida evolución y con una rara forma de comienzo, como una encefalopatía hiperamoniémica. El hepatocarcinoma fibrolamelar es un tumor hepático raro, que se presenta en pacientes jóvenes, sin antecedentes de hepatopatía viral o cirrótica. Su etiología es desconocida, y tradicionalmente fue considerado como de mejor pronóstico que el carcinoma hepatocelular clásico.

We present the case of a young woman, 22 years old, with an aggressive form of fibrolamellar hepatocellular carcinoma. She began with the signs and symptoms of a hyperammonemic encephalopathy, an uncommon form of presentation. Fibrolamellar carcinoma is a rare liver tumor, which affects young patients without previous liver disease. Its etiology is unknown, and it has been considered as a tumor with a better prognosis than the classic hepatocellular carcinoma.

Hyperammonemia in a Patient with Late-Onset Ornithine Carbamoyltransferase Deficiency

Ornithine carbamoyltransferase (OTC) deficiency is a urea cycle disorder that causes the accumulation of ammonia, which can lead to encephalopathy. Adults presenting with hyperammonemia who are subsequently diagnosed with urea cycle disorders are rare. Herein, we report a case of a late-onset OTC deficient patient who was successfully treated with arginine, benzoate and hemodialysis. A 59-yr-old man was admitted to our hospital with progressive lethargy and confusion. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. A plasma amino acid and urine organic acid analysis revealed OTC deficiency. Despite the administration of a lactulose enema, the patient's serum ammonia level increased and he remained confused, leading us to initiate acute hemodialysis. After treatment with arginine, sodium benzoate and hemodialysis, the patient's serum ammonia level stabilized and his mental status returned to normal.

Carnitine-acylcarnitine translocase deficiency. Clinical course of three Saudi children with a severe phenotype

Carnitine-acylcarnitine translocase [CACT] deficiency [McKusick 212138] is a rare life threatening disorder characterized by hypoketotic hypoglycemia, hyperammonemia, encephalopathy, cardiomyopathy hepatopathy, and myopathy. Here, we present a detailed clinical course of 3 Saudi siblings with a severe phenotype. The third patient was described in more detail. Early medical intervention in the form of 25% dextrose intravenous infusion and carnitine supplement followed by a gradual introduction of a high carbohydrate low fat special formula resulted in a good clinical and biochemical response to the treatment in our patient. However, early nephrocalcinosis, severe hypotonia, and subsequently intravascular cerebral accident could not be prevented. He died at 18 months of age as a result of metabolic decompensation. This suggests that CACT deficiency is still a lethal disorder even with an early and aggressive medical intervention

novel mutation in ARG1 gene is responsible for arginase deficiency in an Asian family

Argininemia is a rare autosomal recessive metabolic disorder caused by a deficiency in the arginase enzyme, which is the final enzyme in the urea cycle and responsible for the hydrolysis of arginine to urea and ornithine. The disease becomes symptomatic during childhood and is characterized by progressive spastic quadriplegia, progressive mental impairment, growth retardation, and periodic episodes of hyperammonemia. At least 19 distinct mutations in the ARG1 gene have been identified indicating the molecular heterogeneity of this condition. We report a homozygous novel mutation [c.93 delG] in the ARG1 gene from 3 affected children of a Pakistani family living in the United Arab Emirates. The mutation is expected to lead to a frame shift after the thirtieth residue and a stop codon at residue 44 [p.T30fsX14]. Therefore, this mutation is expected to result in complete loss-of-function of the arginase enzyme and therefore is the mostly likely cause of argininemia in this family

Hyperammonemia: an unusual presenting feature of multiple myeloma.

A 76 year old lady presented with altered sensorium and was found to have hyperammonemia on evaluation. She had no evidence of liver disease. For her symptomatology of backache, evaluation by bone marrow study showed evidence of multiple myeloma. She was given chemotherapy for multiple myeloma, which resulted in improvement in her sensorium, along with this there was also a rapid decline in serum ammonia levels. Hyperviscosity and hypercalcemia are common causes of altered sensorium in a patient with myeloma but in this case hyperammonemia was the likely cause.

Hyperammonemia with citrullinemia.

Two cases of hyperammonemia with elevated citrulline are reported, one resulting from a deficiency of pyruvate carboxylase and the other from a partial deficiency of argininosuccinate synthetase. Diagnosis was based on clinical, biochemical and amino acid profiles. The utility of amino acid determinations in hyperammonemia suspected to underlie an inborn error of metabolism is emphasized.

Helicobacter pylori and hepatic encephalopathy.

Several extra-intestinal diseases have been associated with Helicobacter pylori infection. Hepatic encephalopathy has been linked to H. pylori infection because of the ammonia produced by the organism in the stomach. H. pylori infection is commoner in cirrhotic patients with hepatic encephalopathy than in those without. Increased ammonia levels have been observed in the gastric juice and blood more commonly in cirrhotics with H. pylori infection than in those without. Though the amount of ammonia produced by H. pylori may be too small to contribute to hepatic encephalopathy, eradication of H. pylori has been shown to improve the blood ammonia levels and hepatic encephalopathy.

Effect of Helicobacter pylori eradication on serum ammonia levels in patients with chronic liver disease.

BACKGROUND: Helicobacter pylori infection has been implicated in the development of encephalopathy in chronic liver disease (CLD); this is possibly due to increased production of ammonia by the action of bacterial urease on urea in the gastric lumen. AIM: To evaluate whether H. pylori eradication in patients with CLD affects arterial ammonia levels. METHODS: Forty-six patients with CLD (40 alcoholic, 6 post hepatitis B; Child's class A 7, B 17, C 22) and 36 patients with symptoms of acid-peptic disease (APD) underwent gastrointestinal endoscopy and biopsy; gastric biopsies were evaluated for H. pylori status using rapid urease test and histology. H. pylori-positive subjects received quadruple-drug eradication therapy for 2 weeks. Fasting arterial plasma ammonia levels were estimated before and after eradication of H. pylori. RESULTS: H. pylori infection was present in 21 of 46 (45.7%) patients with CLD and 23 of 36 (63.9%) with APD. At baseline, mean (SD) ammonia levels were higher in the CLD group (97.4 [10.9] versus 81.3 [7.7] mcg/dL in the APD group; p = 0.0001), irrespective of H. pylori status. Amongst patients with liver disease, arterial ammonia levels were similar in the H. pylori-positive and -negative patients (94.1 [9.7] and 100.2 [11.3] mcg/dL, respectively); however, ammonia levels were higher in patients in Child's class C (102.7 [11.4] mcg/dL/dL) than in those in class A (88.4 [1.6] mcg/dL; p < 0.002) or B (94.1 [9.7] mcg/dL; p < 0.002). In patients with APD, ammonia levels were higher in H. pylori-positive patients (85.3 [6.4] versus 74.1 [3.3] mcg/dL; p < 0.001). After eradication of H. pylori infection, ammonia levels decreased to 88.4 (10.0) mcg/dL in CLD and 76.7 (4.8) mcg/dL in APD (p = 0.001 as compared to baseline). There was no difference in post-eradication ammonia levels between Child's classes. CONCLUSION: Levels of arterial blood ammonia are higher in CLD than in APD, and correlate with severity of liver disease. H. pylori eradication was associated with reduction in arterial ammonia levels in patients with CLD.