ABSTRACT
Objective To introduce a case of ethylmalonic encephalopathy which is an autosomal recessive metabolic disorder caused by mutations in the ETHE1 gene. Methods The clinical course and gene mutation in a case of ethylmalonic encephalopathy was retrospectively analysed. Results A previously healthy girl presented with intractable diarrhea from the age of 7 months. Since then, progressive psychomotor regression has been observed. When she was 23 months, her blood butyr-ylcarnitine was signiifcantly increased (4.48μmol/L vs. normal range 0.0~1.0μmol/L), and isovalerylcarnitine (0.70μmol/L vs. normal range 0.0~0.65μmol/L) was also elevated. Her urine levels of ethylmalonic acid and methylsuccinate acid were markedly increased. Cranial MRI revealed bilateral basal ganglia lesions supporting the diagnosis of ethylmalonic encephalopathy. On her ETHE1 gene, a reported mutation (c.488G>A, p.R163Q) and a novel mutation (c.203T>C, p.L68P) were identiifed. After lactose-free dietary treatment and the supplements of L-carnitine, coenzyme Q10, vitamins B1, B2 and C, gradual improvement in general condition, intelligence and motor development has been observed. Conclusions Ethylmalonic aciduria is common in the patients with inborn errors of mitochondrial fatty acid beta-oxidation. In ethylmalonic encephalopathy, elevated blood levels of butyrylcarnitine and isovalerylcarnitine are common and ETHE1 sequencing is helpful in its diagnosis.
ABSTRACT
Introduction: Short-chain acyl-CoA dehydrogenase (SCAD) is a homotetrameric mitochondrial flavoenzyme that catalyzes the initial reaction in short-chain fatty acid b-oxidation. The SCAD gene is located on chromosome 12q22 and is approximately 13 kb long with 10 exons and 1236 nucleotides of coding sequence. Hereditary SCAD deficiency has been reported and only a few cases of this disorder have been described. Objective: The present study was conducted to determine the possible presence of the 625G>A variation in the short-chain acyl-CoA dehydrogenase gene in Caldas (Colombia), given that variations 625G>A and 511C>T are present in 14% of some studied populations; thereby sometimes causing its deficiency. Methods: This is a descriptive study; blood samples from three-hundred adult volunteers were tested for 625G>A polymorphism, analysing the polymerase chain reaction amplified cDNA, using a single-stranded conformation polymorphism assay. The results were confirmed by direct bidirectional cycle sequencing using DNA from the positive persons. Results: The polymorphism was identified and confirmed in four healthy persons. Conclusion: This is evidence of the presence of 625G>A polymorphism in the short-chain acyl-CoA dehydrogenase gene in Colombia, meaning that some people in our populations can be at risk of suffering SCAD deficiency and its main complication: the ethylmalonic aciduria.
Introducción: La acil-CoA deshidrogenasa de cadena corta (SCAD) es una flavoenzima homotetramérica mitocondrial que cataliza la reacción inicial de la â-oxidación de los ácidos grasos de cadena corta. El gen SCAD se ubica en el cromosoma 12q22, con una longitud de 13 kb, con 10 exones y 1236 nucleótidos de secuencia codificadora. Se ha informado la deficiencia hereditaria de SCAD y se han descrito pocos casos de la deficiencia. Objetivo: El presente estudio buscó determinar la posible presencia del polimorfismo 625G>A en Caldas, Colombia, debido a que las variantes 625G>A y 511C>T en el gen de la acil-CoA deshidrogenasa de cadena corta están presentes en 14% de algunas poblaciones estudiadas, causando algunas veces su deficiencia. Métodos: El presente estudio es descriptivo; se estudiaron muestras de sangre de 300 voluntarios para el polimorfismo 625G>A mediante la técnica de polimorfismo de conformación de la cadena simple, con ADN amplificado por reacción en cadena de la polimerasa. Los resultados se confirmaron por secuenciación. Resultados: El polimorfismo se identificó en cuatro personas aparentemente sanas. Conclusión: Existe evidencia de la presencia del polimorfismo 625 G>A en el gen de la acil-CoA en Colombia, lo que significa que algunas personas en la poblaciones del país pueden estar en riesgo de sufrir deficiencia de SCAD y su principal complicación, la aciduria etilmalónica.