RESUMO
D-2-hydroxyglutaric aciduria (D-2-HGA) is a cerebral organic aciduria characterized by the accumulation of abnormal amounts of D-2-hydroxyglutaric acid in cerebrospinal fluid, blood, and urine. The clinical phenotype varies widely from neonatal severe epileptic encephalopathy to asymptomatic. Magnetic resonance imaging of affected patients typically show signs of delayed cerebral maturation, ventricular abnormalities and the presence of sub-ependymal cysts in the first months of life. We present clinical, biochemical and brain magnetic resonance imaging data of two pediatric patients with D-2-hydroxyglutaric aciduria. One patient presented with severe early infantile-onset epileptic encephalopathy, marked hypotonia, visual deficit, developmental delay and abnormal neuroradiological findings; while the other had hypotonia and development delay. Our findings reinforce the described phenotype of this rare neurometabolic inherited disorder. The diagnostic approach is based on clinical findings and the neuroimaging pattern and is established by the detection of D-2-hydroxyglutaric acid in body fluids. We suggest considering D-2-hydroxyglutaric aciduria in the differential diagnosis of any neonate or infant with epileptic encephalopathy and CNS dysfunction of unknown origin.
Assuntos
Encefalopatias Metabólicas Congênitas/urina , Glutaratos/urina , Anticonvulsivantes/uso terapêutico , Atrofia , Encéfalo/anormalidades , Encéfalo/patologia , Encefalopatias Metabólicas Congênitas/complicações , Encefalopatias Metabólicas Congênitas/diagnóstico , Encefalopatias Metabólicas Congênitas/tratamento farmacológico , Encefalopatias Metabólicas Congênitas/genética , Encefalopatias Metabólicas Congênitas/patologia , Carnitina/uso terapêutico , Pré-Escolar , Consanguinidade , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Deficiência Intelectual/etiologia , Hipotonia Muscular/etiologia , Transtornos Psicomotores/etiologia , Riboflavina/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/etiologiaRESUMO
La aciduria D-2-hidroxiglutárica (D-2-HGA), es una aciduria orgánica cerebral, caracterizada por la acumulación de concentraciones anormales de ácido D-2-hidroxiglutárico en orina, sangre y líquido cefalorraquídeo. El fenotipo clínico es variable, observándose desde una encefalopatía epiléptica severa hasta una forma asintomática. Las imágenes de resonancia magnética de los pacientes afectados, frecuentemente muestran signos de retardo en la maduración cerebral, anomalías ventriculares y la presencia de quistes subependimarios en los primeros meses de vida. A continuación presentamos las alteraciones clínicas, bioquímicas y de neuroimagen de dos pacientes con aciduria D-2-hidroxiglutárica. Uno de los pacientes se presentó con una encefalopatía epiléptica severa de inicio temprano, marcada hipotonía, déficit visual, retardo en el desarrollo y signos neuroradiológicos anormales. El segundo paciente presentó hipotonía severa y retardo psicomotor. Nuestros hallazgos refuerzan el fenotipo descrito de este desorden neurometabólico hereditario poco frecuente. El diagnóstico se fundamentó en las alteraciones clínicas y el patrón de neuroimagen y se confirmó con la detección del ácido D-2-hidroxiglutárico en fluidos biológicos. Sugerimos considerar la aciduria D-2-hidroxiglutárica en el diagnóstico diferencial de todo recién nacido o lactante con encefalopatía epiléptica y disfunción del CNS de origen desconocido.
D-2-hydroxyglutaric aciduria (D-2-HGA) is a cerebral organic aciduria characterized by the accumulation of abnormal amounts of D-2-hydroxyglutaric acid in cerebrospinal fluid, blood, and urine. The clinical phenotype varies widely from neonatal severe epileptic encephalopathy to asymptomatic. Magnetic resonance imaging of affected patients typically show signs of delayed cerebral maturation, ventricular abnormalities and the presence of sub-ependymal cysts in the first months of life. We present clinical, biochemical and brain magnetic resonance imaging data of two pediatric patients with D-2-hydroxyglutaric aciduria. One patient presented with severe early infantile-onset epileptic encephalopathy, marked hypotonia, visual deficit, developmental delay and abnormal neuroradiological findings; while the other had hypotonia and development delay. Our findings reinforce the described phenotype of this rare neurometabolic inherited disorder. The diagnostic approach is based on clinical findings and the neuroimaging pattern and is established by the detection of D-2-hydroxyglutaric acid in body fluids. We suggest considering D-2-hydroxyglutaric aciduria in the differential diagnosis of any neonate or infant with epileptic encephalopathy and CNS dysfunction of unknown origin.