Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Ann Neurol ; 85(3): 385-395, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30635937

RESUMO

OBJECTIVE: SLC13A3 encodes the plasma membrane Na+ /dicarboxylate cotransporter 3, which imports inside the cell 4 to 6 carbon dicarboxylates as well as N-acetylaspartate (NAA). SLC13A3 is mainly expressed in kidney, in astrocytes, and in the choroid plexus. We describe two unrelated patients presenting with acute, reversible (and recurrent in one) neurological deterioration during a febrile illness. Both patients exhibited a reversible leukoencephalopathy and a urinary excretion of α-ketoglutarate (αKG) that was markedly increased and persisted over time. In one patient, increased concentrations of cerebrospinal fluid NAA and dicarboxylates (including αKG) were observed. Extensive workup was unsuccessful, and a genetic cause was suspected. METHODS: Whole exome sequencing (WES) was performed. Our teams were connected through GeneMatcher. RESULTS: WES analysis revealed variants in SLC13A3. A homozygous missense mutation (p.Ala254Asp) was found in the first patient. The second patient was heterozygous for another missense mutation (p.Gly548Ser) and an intronic mutation affecting splicing as demonstrated by reverse transcriptase polymerase chain reaction performed in muscle tissue (c.1016 + 3A > G). Mutations and segregation were confirmed by Sanger sequencing. Functional studies performed on HEK293T cells transiently transfected with wild-type and mutant SLC13A3 indicated that the missense mutations caused a marked reduction in the capacity to transport αKG, succinate, and NAA. INTERPRETATION: SLC13A3 deficiency causes acute and reversible leukoencephalopathy with marked accumulation of αKG. Urine organic acids (especially αKG and NAA) and SLC13A3 mutations should be screened in patients presenting with unexplained reversible leukoencephalopathy, for which SLC13A3 deficiency is a novel differential diagnosis. ANN NEUROL 2019;85:385-395.


Assuntos
Ácido Aspártico/análogos & derivados , Ácidos Cetoglutáricos/metabolismo , Leucoencefalopatias/genética , Simportadores/genética , Adolescente , Ácido Aspártico/líquido cefalorraquidiano , Ácido Aspártico/metabolismo , Pré-Escolar , Feminino , Células HEK293 , Humanos , Ácidos Cetoglutáricos/líquido cefalorraquidiano , Ácidos Cetoglutáricos/urina , Leucoencefalopatias/metabolismo , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Mutação de Sentido Incorreto , Linhagem , Infecções Respiratórias , Ácido Succínico/metabolismo , Simportadores/metabolismo , Tonsilite , Sequenciamento do Exoma
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa