Neuropediatría

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.

Long‑term clinical results of the Flow ventricular catheter for hydrocephalus: brief report.

2025-06-02T16:12:08Z

Long‑term clinical results of the Flow ventricular catheter for hydrocephalus: brief report. Galarza, Marcelo; Sosa, Fidel; Etus, Volkan; Argañaraz, Romina; Gazzeri, Roberto; Giménez, Ángel; Amigó, José María

Spinal Cord UBOs in NF1 Pediatric Patients: Single Institution Experience

2025-01-06T17:40:37Z

Spinal Cord UBOs in NF1 Pediatric Patients: Single Institution Experience Lombardi, Francina; Aguilar, Martín Santiago; Palomar, Nicolás; Carnevale, Martín Diego; Vigliano, Alejandra; Casola, A.; Schteinschnaider, Ángeles; Diez, Blanca Introduction: Neurofibromatosis type 1 (NF1) is a neurocutaneous disease that shows specific clinical characteristics and imaging. Being a predisposition syndrome to diferent tpes of tumors, neurofibromas and glioma of the optic pathway being the most common lesions. It is essential to know the typical, non-oncological lesions that can be present and diagnosed through neuroimaging, so that they are not missdiagnosed and treated incorrectly. Within these lesion we foun UBOs (Unidentified bright objects), located on white matter areas in the parenchyma, but little taken into account at spinal cord level. Aims: To describe the prevalence of UBOs located in the spinal cord, in patients with NF1 during childhood, based on data obtained at our institution. Materials and methods: Retrospective, observational and descriptive study of patients between 2 and 21 years old with NF1 diagnosis, evaluated during 2009 to 2023 time period, who had whole brain and spinal cord MRI (n=32). The presence of UBOs was evaluated. We refer to spinal UBO as single or multiple lesions located in the cord, hyperintense on T2/STIR sequences and isointense on T1, without gadolinium enhancement or mass effect. Results: Male patient 58.3%, with an average age of 13.1 years. Twenty seven patients (79%) had brain UBOs and 9 (26.4%) Spinal cord UBOs. Of the latter, 44.4% presented a single spinal cord lesion, the rest had more than one. The most comon location was the subaxial cervical (C3-T1) area, followed by the cervical superior (C1-C2) area, dorsal with 2 lesions and conus medullaris in only one case. In all of them, hypersignal was found in T2 sequence and isointense signal in T1; no case showed enhancement with intravenous contrast or mass effect. There was coexistence of brain UBOs in all our patients. None of the patients presented clinical manifestations associated with these lesions. Conclusion: There is little literature regarding the existence of spinal UBOs. It is important to recognize the existence and diagnostic imaging characteristics of these in order to avoid diagnostic and therapeutic errors regarding the presence of spinal cord lesion in NF1 patients.