Manejo inicial de la hiperamonemia aguda en pediatría / Initial management of acute hyperammonemia in pediatrics

La hiperamonemia constituye una emergencia médica. No existen publicaciones que hagan referencia a la disponibilidad de recursos, insumos y conocimientos necesarios para el manejo inicial de esta por parte del pediatra en nuestro país, pero, según la experiencia de los autores, los recursos necesarios no se encuentran disponibles los 365 días del año en una gran porción de nuestro territorio. Sobre la base de este estado de situación, de una revisión bibliográfica internacional sobre el tema y de la experiencia de los autores, se elaboraron una serie de recomendaciones para el manejo pediátrico inicial de esta emergencia, que tienen como objetivo poder reducir las deficiencias, permitir una sospecha clínica adecuada que lleve a un diagnóstico y tratamiento de emergencia oportunos, con utilización racional de recursos farmacológicos (algunos de ellos de alto costo), para reducir la morbimortalidad que asocia la patología.

Hyperammonemia is a medical emergency. There are no publications regarding the availability of resources, supplies, and knowledge necessary for the initial management of hyperammonemia by pediatricians in Argentina; however, according to the authors' experience, the necessary resources are not available all year round in a large portion of our territory. Based on such state of affairs, an international bibliographic review on this topic and the authors' experience, we developed a series of recommendations for the initial pediatric management of this emergency, with the objective of reducing deficiencies, allowing adequate clinical suspicion leading to a timely diagnosis and emergency management and a rational use of pharmacological resources (some of which are costly) to reduce the morbidity and mortality associated with hyperammonemia.

Analysis of blood carnitine profile and SLC22A5 gene variants in 17 neonates with Primary carnitine deficiency / 中华医学遗传学杂志

OBJECTIVE@#To analyze the blood free carnitine (C0) level and SLC22A5 gene variants in 17 neonates with Primary carnitine deficiency (PCD) and to determine its incidence in local area and explore the correlation between C0 level and genotype.@*METHODS@#148 043 newborns born in 9 counties (cities and districts) of Ningde city from September 2016 to June 2021 were selected as study subjects. Blood free carnitine and acyl carnitine of 148 043 neonates were analyzed. Variants of the SLC22A5 gene were screened in those with blood C0 < 10 µmol/L, or C0 between 10 ∼ 15 µmol/L. Correlation between the free carnitine level and genetic variants was analyzed.@*RESULTS@#In total 17 neonates were diagnosed with PCD, which yielded a prevalence of 1/8 707 in the region. Twelve variants of the SLC22A5 gene were identified, with the common ones including c.760C>T, c.1400C>G and c.51C>G. Compared with those carrying other variants of the gene, children carrying the c.760C>T variant had significantly lower C0 values (P < 0.01).@*CONCLUSION@#The prevalence of PCD is relatively high in Ningde area, and intervention measures should be taken to prevent and control the disease. The c. 760C>T variant is associated with lower level of C0, which can provide a clue for the diagnosis.

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.

Hiperamonemia en niños: clasificación y opciones terapéuticas / Hyperammonaemia in children: classification and therapeutic options

La hiperamonemia se presenta en forma secundaria por aumento en la producción de amonio, como en la hemorragia gastrointestinal o disminución de la eliminación, como ocurre en errores innatos del metabolismo, principalmente en aquellos con defectos en el ciclo de la urea, insuficiencia hepática o fármacos. Clasificar la hiperamonemia y reportar las opciones terapéuticas en niños, su abordaje clínico y revisión de la literatura. Estudio prospectivo, descriptivo y transversal de niños con hiperamonemia. Variables: edad, género, etiología, niveles de amonio, clínica, tratamiento. 21 pacientes, 12 (57,12%) varones y 9 (42,88%) hembras. Edad promedio 3,91 años (rango:<1mes-14 años). Amonio promedio general 214,66 mmol/l (rango:110-980), clasificados según severidad: sin insuficiencia hepática 11/21 con promedio de amonio 99,44 y 201 mmol/l en hiperamonemia leve y moderada respectivamente. Clínica y laboratorio de insuficiencia hepática en 10/21 con promedio de amonio de 114,44, 287,51 y 756,66 en leve, moderada y severa hiperamonemia, con una diferencia significativa entre el nivel de amonio y la presencia o ausencia de insuficiencia hepática (p<0,0001); 5/10 con insuficiencia hepática ingresaron a terapia intensiva, 4 de ellos presentaron encefalopatía hepática, un paciente fallecido. Etiología: Error innato del metabolismo 33,33%, toxicidad por medicamentos 23,80%, hepatitis viral A fulminante 19,04% y otros virus 9,52%, hepatitis autoinmune 4,76% y urosepsis 4,76%. En los casos leves-moderados se administró lactulosa dosis respuesta vía oral 19/21 y por enema rectal 7/21 con L-carnitina en 15/21 y en Hiperamonemia severa adicionalmente Benzoato de sodio en 4/21 y hubo indicación de hemodiálisis en 3 pacientes. Restricción proteica en todos, vitaminoterapia y 6 niños tratados con ácido ursodeoxicólico. La hiperamonemia es multifactorial, requiere diagnóstico temprano, la clasificación de severidad permite el tratamiento oportuno para evitar complicaciones....

Hyperammonaemia occurs secondarily by increased production of ammonia, as gastrointestinal bleeding or decreased elimination, as occurs in inborn errors of metabolism, especially in those with defects in the urea cycle, liver failure or drugs. To classify the report hyperammonaemia and therapeutic options in children, its clinical approach and review of the literature. Prospective, descriptive and transversal children with hyperammonaemia. Variables: age, gender, etiology, ammonia levels, clinical treatment. 21 patients, 12 (57,12%) males and 9 (42,88%) females. Mean age 3,91 years (range: <1m-14a). ammonium 214,66 mmol / l (range :110-980), classified according to severity: no hepatic impairment 11/21 with 99,44 average ammonium and 201 mmol / l in Hyperammoanemia mild and moderate respectively. Clinical and laboratory liver failure 10/21 with ammonium averaging 114,44, 287,51 and 756,66 as mild, moderate and severe hyperammonemia, with a significant difference between the level of ammonia and the presence or absence of liver failure (p < 0,0001), 5/10 with liver failure admitted to intensive care, 4 of them had hepatic encephalopathy, a patient died. Etiology: An inborn error of metabolism 33,33%, 23,80% drug toxicity, fulminant viral hepatitis and other viruses 19,04% 9,52% 4,76% autoimmune hepatitis and urosepsis 4,76%. In mild-moderate cases were given oral lactulose Dose 19/21 and by enema rectal 7/21 with L-carnitine in 15/21 and further severe Hyperammonemia sodium benzoate 4/21 and was indication of hemodialysis in 3 patients. Protein restriction at all, vitamin therapy and 6 children treated with ácidoursodeoxicólico. Hyperammonemia is multifactorial, requires early diagnosis, classification of severity allows early treatment to avoid complications and development of irreversible neurological sequelae

Embolization of congenital intrahepatic porto-systemic shunt by n-butyl cyanoacrylate.

Congenital intrahepatic portosystemic venous shunt (IHPSVS) is rare vascular anomaly. We present one case of a 14- month male child who presented with global developmental delay. Child had high ammonia levels with low glutamine and high bile salts on the previous investigations and had history of neonatal seizures since day 13 of life. On admission, serum ammonia levels were elevated to 112μmol/L. Other laboratory investigations including liver and renal function test, and electrolytes were normal. He was, diagnosed to have IHPSVS on the basis of Doppler and CT, and treated by embolization with n-butyl cyanoacrylate (glue). A brief review of diagnostic modalities and endovascular management for the IHPSVS is presented including the present case.

Congenital hypopituitarism associated with hyperammonemia.

Neonatal onset hypopituitarism is a life threatening but potentially treatable metabolic condition. However, in the majority of cases it can be fatal due to the metabolic disturbances. We report a newborn with profound symptomatic hypoglycemia and hyperammonemia who initially was thought to have an inborn error of metabolism (IEM). After an initial falsely reassuring magnetic resonance imaging (MRI) brain scan, further endocrine investigation eventually led to the correct diagnosis and treatment.

Encefalopatía asociada a Valproato / Val proate-associated hyperammonemic encephalopathy. Report of one case

Valproate can be associated to hyperammonemic encephalopathy, characterized by fluctuating sudden-onset alterations of sensorium, focal symptoms and an increase in the frequency of seizures. We report a 78 year-old female using valproate 1,000 mg/ day for 10 months for the treatment to tonic-clonic seizures. She was admitted on three occasions in the last fourth months for self limited clouding of sensorium. Laboratory, imaging and electroencephalografic studies were non-contributory Blood ammonia levels were 123 fig/dl (normal: 15-50 fig/dl). Due to the possibility of a hyperammonemic encephalopathy secondary to valproate, the drug was discontinued and she was treated with lactulose and intravenous L-carnitine, 1 g/day The patient showed a complete recovery within 48 hours. This drug-associated encephalopathy is a reversible but potentially fatal cause, probably underdiagnosed, that requires a high index of suspicion.

Role of Helicobacter pylori infection in hyperammonemia and subclinical hepatic encephalopathy in cirrhosis of liver.

INTRODUCTION: Gastric Helicobacter pylori infection is believed to be associated with a higher risk of hepatic encephalopathy among patients with cirrhosis of liver. However, the role of this infection in causation of subclinical hepatic encephalopathy has not been studied in detail. METHODS: Patients with cirrhosis of liver but no hepatic encephalopathy underwent venous blood ammonia measurement, psychometric tests (number connection tests [NCT] and figure connection tests [FCT]), and gastric biopsies for presence of H. pylori infection. The results of blood ammonia and psychometric tests in the H. pylori-positive and -negative study subjects were compared. RESULTS: Of 58 patients with liver cirrhosis studied, 31 had evidence of gastric H. pylori infection. Venous blood ammonia levels were comparable in patients with (median 29 mmol/L; range 18-47) and without (34 [15-48] mmol/L; p=ns) H. pylori infection. The time taken to complete NCT trail A (median 37 s [range 25-69] versus 36.5 [26-62]), NCT trail B (64 s [48-91] versus 63.5 [42-88]), FCT trail A (59 s [31-115] versus 58 [38-590]) and FCT trail B (76 s [55-187] versus 82 [36-125]) were similar in those with and those without H. pylori infection. For each of the four tests, the proportion of subjects with abnormal test results was similar among H. pylori-positive and -negative subjects. CONCLUSION: Presence of H. pylori infection among patients with cirrhosis of liver but no overt hepatic encephalopathy is not associated with increase in blood ammonia concentration or deterioration in psychomotor function.