Classic and Atypical Late Infantile Neuronal Ceroid Lipofuscinosis in Latin America: Clinical and Genetic Aspects, and Treatment Outcome with Cerliponase Alfa.

Introduction: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), is a neurodegenerative autosomal recessive disease caused by TPP1 gene variants, with a spectrum of classic and atypical phenotypes. The aim of treatment is to slow functional decline as early as possible in an attempt to improve quality of life and survival. This study describes the clinical characteristics as well as the response to treatment with cerliponase alfa. Materials and methods: A retrospective study was conducted in five Latin-American countries, using clinical records from patients with CLN2. Clinical follow-up and treatment variables are described. A descriptive and bivariate statistical analysis was performed. Results: A total of 36 patients were observed (range of follow-up of 61-110 weeks post-treatment). At presentation, patients with the classic phenotype (n = 16) exhibited regression in language (90%), while seizures were the predominant symptom (87%) in patients with the atypical phenotype (n = 20). Median age of symptom onset and time to first specialized consultation was 3 (classical) and 7 (atypical) years, while the median time interval between onset of symptoms and treatment initiation was 4 years (classical) and 7.5 (atypical). The most frequent variant was c.827 A > T in 17/72 alleles, followed by c.622C > T in 6/72 alleles. All patients were treated with cerliponase alfa, and either remained functionally stable or had a loss of 1 point on the CLN2 scale, or up to 2 points on the Wells Cornel and Hamburg scales, when compared to pretreatment values. Discussion and conclusion: This study reports the largest number of patients with CLN2 currently on treatment with cerliponase alfa in the world. Data show a higher frequency of patients with atypical phenotypes and a high allelic proportion of intron variants in our region. There was evidence of long intervals until first specialized consultation, diagnosis, and enzyme replacement therapy. Follow-up after the initiation of cerliponase alfa showed slower progression or stabilization of the disease, associated with adequate clinical outcomes and stable functional scores. These improvements were consistent in both clinical phenotypes.

Aciduria L-2-hidroxiglutárica. A propósito de un caso / L-2-hydroxyglutaric aciduria. A case report

L-2-hydroxyglutaric aciduria (AL2HG) is a rare autosomal recessive neurometabolic disorder. It is characterized by elevated of L-2-hydroxyglutarate and lysine in urine, cerebrospinal fluid and plasma. Patients usually have neurological manifestations including mild to moderate psychomotor developmental delay, cerebellar ataxia, macrocephaly and epilepsy. Magnetic resonance imaging (MRI) has shown abnormalities in the signal intensity of the subcortical cerebral white matter, putamen and dentate nucleus. This article reports a case to demonstrate the classically described imaging findings.

La aciduria L-2-hidroxiglutárica (AL2HG) es un raro trastorno neurometabólico de tipo autosómico recesivo. Se caracteriza por niveles elevados de L-2-hidroxiglutarato y lisina en orina, líquido cefalorraquídeo y plasma. Los pacientes suelen tener manifestaciones neurológicas que incluyen retraso en el desarrollo psicomotor de leve a moderado, ataxia cerebelosa, macrocefalia y epilepsia. En resonancia magnética (RM) se han descrito anormalidades en la intensidad de señal de la sustancia blanca cerebral subcortical, el putamen y el núcleo dentado. En este artículo se presenta un caso para demostrar los hallazgos por imagen que se describen clásicamente.

Características clínicas y sociodemográficas de niños menores de 13 años con diagnóstico confirmado de tuberculosis pulmonar o sin él, en el Hospital Universitario San Vicente de Paúl, Medellín, Colombia, 2007-2008 / Clinical and sociodemographic characteristics of children, younger than13 years, with or without a confirmed diagnosis of pulmonary tuberculosis, at Hospital Universitario San Vicente de Paúl, Medellín, Colombia, 2007-2008

Introducción: la tuberculosis (TB) es una de las enfermedades infectocontagiosas más importantes en el mundo debido a que se asocia con altas tasas de morbilidad y mortalidad. En niños puede afectar cualquier órgano o sistema, a cualquier edad, pero con mayor frecuencia es pulmonar. Tiene graves consecuencias si no se la diagnostica y trata de forma oportuna y adecuada. Los síntomas y signos son variados e inespecíficos lo que, sumado a la dificultad en el aislamiento del Mycobacterium tuberculosis a partir de muestras de niños disminuye la probabilidad de hacer el diagnóstico. Objetivo: puntualizar las características clínicas y sociodemográficas de un grupo de niños con sospecha o diagnóstico final de tuberculosis pulmonar. Metodología: la población en estudio correspondió a 56 niños menores de 13 años atendidos en los servicios pediátricos de urgencias y hospitalización del Hospital Universitario San Vicente de Paúl, en Medellín, a quienes se les sospechó o confirmó TB pulmonar, según los criterios de la OMS, entre julio de 2007 y diciembre de 2008. Se aplicó un formulario para la recolección de los datos, que se obtuvieron directamente de los pacientes o sus acudientes, y se completaron con las historias clínicas en el archivo del hospital. Resultados: en 38 de los 56 niños (67,9%) se confirmó el diagnóstico de tuberculosis pulmonar. El 87,5% pertenecían a los estratos socioeconómicos más bajos (1 y 2); 55% provenían del área urbana de Medellín, 70% eran mestizos y 28,6%, indígenas. La tos y la fiebre fueron las manifestaciones más comunes en el grupo con diagnóstico definitivo de TB; el criterio epidemiológico fue positivo en 53,6% de los casos, el radiológico en 51,8% y el tuberculínico, en 41,1%. Conclusión: la TB pulmonar sigue presente en la población infantil y se debe tener un alto índice de sospecha clínica para detectarla, pues las manifestaciones son variadas e inespecíficas...

Introduction: Worldwide, tuberculosis is one of the most important infectious and contagious diseases. It is associated with high morbidity and mortality rates. In children, tuberculosis is most frequently pulmonary but it may affect every organ and system. Its consequences, if inadequately treated, may be severe. Symptoms and signs are diverse and nonspecific, and the bacteriological confirmation is difficult in children. For these reasons, making the diagnosis in the pediatric population may be a really difficult challenge.Objective: To determine the sociodemographic and clinical characteristics of a group of children with suspicion or confirmed diagnosis of pulmonary tuberculosis.Methodology: Fifty six children were studied at Hospital Universitario San Vicente de Paúl, in Medellín, Colombia, between July 2007 and December 2008. Pulmonarytuberculosis was confirmed according to the WHO criteria. Information was obtained from the patients themselves, their parents, and the hospital files. Results: In 38 of the 56 children (67.9%) pulmonary tuberculosis was confirmed. Their socioeconomic situation was poor in 87.5% of the cases; 55% came from the urban area of the city; 70% were mestizo, and 26.8%, Indians. Cough and fever were the predominant clinical manifestations. The positivity rate of diagnostic criteria was as follows: 53.6% for the epidemiological, 51.6% for the radiological, and 41.1% for the tuberculin test. Conclusion: Pulmonary tuberculosis continues to be of great importance in the pediatric population...