Neuropediatría.artículos

Lactic acidosis, rhabdomyolysis, and hyperammonemia: Atypical presentation in a new patient with PDE-ALDH7A1 defect

2025-12-03T17:46:52Z

Lactic acidosis, rhabdomyolysis, and hyperammonemia: Atypical presentation in a new patient with PDE-ALDH7A1 defect Bottino, Marina; Boyer, Monica; Steenari, Maija R.; Barrick, Rebekah; Abdenur, Jose E. Pyridoxine-Dependent Epilepsy (PDE) is an autosomal recessive disorder caused by biallelic variants in ALDH7A1. The most common presentation is intractable seizures in the neonatal/early infantile period, which respond to pyridoxine. Other manifestations include perinatal asphyxia, hypoglycemia, and neuroimaging abnormalities. Despite early treatment, patients often have neurodevelopmental abnormalities. Treatment guidelines recommend triple therapy with pyridoxine, dietary lysine restriction, and arginine supplementation. We report an individual presenting with laboratory abnormalities suggestive of mitochondrial disease. Born full-term, via NSVD, with normal Apgar scores and cord gases. At 30 min, grunting developed, and at 4 h of life, jerky movements with eye deviation were noted. Laboratory results revealed acidosis (pH 7.15) and increased lactate (11.4 mMol/L, rr <2.1). The patient was started on IV fluids, given 1 mEq/kg of sodium bicarbonate, and transferred for higher-level care. Upon arrival, the evaluation was notable for hypotonia, non-rhythmic jerking movements, rapid eye blinking, and a critically low pH (6.92), high lactate (15.3 mMol/L), hyperammonemia (153 μMol/L, rr < 75), and a creatine kinase level of 15,742 U/L (rr 35-230). A single dose of phenobarbital was given, and the baby was intubated and ventilated. Video electroencephalogram (vEEG) showed a discontinuous background with abnormal, sharply contoured bursts alternating with suppression, with no clinical correlation. The patient was treated with continuous sodium bicarbonate drip and IV fluids, restricting glucose. Abnormal movements, lactic acidosis, and hyperammonemia resolved within 24 h. An electroencephalogram (EEG) at 5 days of life (DOL) showed a mildly discontinuous background with no epileptic activity, and MRI showed a thin corpus callosum, cysts, and cerebellar hypoplasia. Creatine kinase peaked at 30,995 U/L and normalized on DOL 8. Organic acids revealed significant increases in lactate, 2-OH-butyrate, pyruvate, 3-OH-butyrate, 2-OH-isovalerate, and a mild increase in Krebs-cycle intermediates. Rapid whole genome sequence (rWGS) was available on DOL 9, disclosing two variants in ALDH7A1: c.1559C > T p.Ser520Phe, previously reported, and c.1540 A > G p.Lys514Glu, considered a VUS. Treatment with pyridoxine started at 30 mg/kg/day. Pre-treatment biomarkers were consistent with the diagnosis of PDE-ALDH7A1: urine Pipecolate 117.8 mMol/mol, RR ≤10, 6-oxo-Pipecolate 8.4 mMol/mol, RR ≤2.0 and plasma alpha-aminoadipic semialdehyde (AASA) 5.2 uMol/L, RR <0.4. Treatment with arginine was added on DOL 10 (200 mg/kg/day) and a lysine-restricted diet on DOL 12, after TPN was discontinued. Clinical exam improved, no seizures were observed, and EEG normalized. PDE biomarkers decreased, and the patient was discharged home on DOL 25. Elevated lactic acid has been reported in up to 70.3 % of PDE-ALDH7A1 patients with neonatal-onset; however, there is limited information about its severity, etiology, or pathophysiologic mechanism. We, therefore, conducted a review of published cases of neonatal-onset PDE-ALDH7A1 whose actual lactic acid values were reported. A total of 12 patients were analyzed and compared to this case. In most instances, a trigger (such as pulmonary hemorrhage, postnatal hypoxia, or status epilepticus) could be identified as the cause of elevated lactic acid; nevertheless, in many individuals, lactic acidosis remained unexplained. This case expands on the biochemical presentation of PDE-ALDH7A1 and highlights the importance of identifying increased lactic acid as another of its manifestations. We also provide evidence to support the reclassification of the c.1540 A > G (p.Lys514Glu) variant as pathogenic.

Resultados de la descanulación en pacientes pediátricos con daño cerebral adquirido: estudio retrospectivo

2025-11-04T16:58:30Z

Resultados de la descanulación en pacientes pediátricos con daño cerebral adquirido: estudio retrospectivo Indo, Juan Ignacio; Ríos, Zelmira; de Nicola, Carla Introducción: La descanulación en pacientes pediátricos con traqueotomía debido a daño cerebral adquirido es un objetivo clave en la rehabilitación, pero existe una falta de consenso acerca del protocolo óptimo y sobre los factores de éxito en la descanulación. Es por esto que el objetivo de este estudio es describir la experiencia de descanulación en un centro de neurorrehabilitación pediátrica en Buenos Aires. Métodos: Estudio observacional, retrospectivo y descriptivo realizado en pacientes menores de 18 años con daño cerebral adquirido y traqueotomía, internados entre enero de 2016 y agosto de 2023. Se recopilaron datos demográficos, clínicos y resultados de fibroendoscopia. La descanulación se llevó a cabo según criterios institucionales y se realizó un monitoreo de 48 horas para evaluar complicaciones posdescanulación. Resultados: De los 41 pacientes incluidos en el estudio, 12 (29.3%) fueron descanulados exitosamente, mientras que 29 (70.7%) fueron dados de alta con válvula fonatoria, cánula ocluida o con la configuración inicial de la traqueotomía. Se realizó fibroendoscopia en 13 pacientes, detectando lesiones en 11 casos. Conclusiones: La tasa de descanulación observada se encuentra dentro del rango documentado en la literatura, aunque cercana al límite inferior, lo que podría deberse a la complejidad de los casos y al enfoque conservador adoptado. La presencia de trastornos de consciencia y comorbilidades fueron factores importantes en el proceso de descanulación.

Estudio epidemiológico de sepsis grave pediátrica en la República Argentina

2023-02-09T00:50:55Z

Estudio epidemiológico de sepsis grave pediátrica en la República Argentina Jabornisky, Roberto; Sáenz, Silvia S.; Capocasa, Patricia; Jaen, Roxana; Moreno, Rodolfo P.; Landry, Luis; Rufach, Daniel; Santos, Silvia N.; Berrueta, Mabel; Carcillo, Joseph; Vassallo, Juan Carlos; Grupo de Investigación Clínica y Epidemiológica en Terapia Intensiva Pediátrica de la Sociedad Argentina de Pediatría Introduction: Severe sepsis (SS) is one of the leading causes of pediatric mortality in Argentina. The objective was to describe the epidemiological characteristics and to analyze risk factors associated with mortality from SS among patients hospitalized in pediatric intensive care units (PICU) in Argentina. Population and methods: Observational, prospective cohort study among patients with SS hospitalized in PICUs in Argentina from 8/1/2008 to 9/30/2008. Results: Two thousand five hundred and fifty nine patients were admitted at 59 PICUs. A total of 315 patients (335 events) were included. Patients' median age was 8 months (1-182). The frequency was 13.8 %, and 28-day mortality was 31.6 %. Patients with a higher mortality were those who were coming from rural areas, had comorbidities at the time of admission or a history of cancer, had shock or acute respiratory distress syndrome (ARDS), were administered low-dose corticosteroids or vasoactive drugs or more than 60 ml/kg of fluid in the first hour and in the first 6hours, and had severe malnutrition. Following adjustment by severity using a multivariate logistic regression model, only coming from a rural area, having shock or ARDS remained associated with 28-day mortality. Forty per cent of patients received antibiotics 60 minutes after diagnosis. Conclusions: SS is an event with a high frequency and mortality in Argentina. In the severity adjusted multivariate analysis, only coming from a rural area, having ARDS and/or shock were associated with higher mortality.