RESUMO
X-linked creatine transporter deficiency is caused by hemizygous or heterozygous pathogenic variants in SLC6A8 that cause neuropsychiatric symptoms because of impaired uptake of creatine into tissues throughout the body. Small cohorts have suggested that supplementation of creatine, arginine, and glycine can stop disease progression in males, but only six cases of supplementation in females have been published. Here, we present a female with a de-novo pathogenic SLC6A8 variant who had ongoing weight loss, mild intellectual disability, and neuropsychiatric symptoms. Magnetic resonance spectroscopy of the brain showed reduced creatine on all acquired spectra. The patient was started on creatine-monohydrate, l -arginine, and l -glycine supplementation, and she had significant symptomatic improvement within the following 3 weeks. After 8 months of supplementation, magnetic resonance spectroscopy showed improved creatine concentrations with normalizing semiquantitative ratios with other brain metabolites. Current data supports clinicians trialing creatine, arginine, and glycine supplements for female patients with creatine transporter deficiency.
Assuntos
Arginina , Creatina , Suplementos Nutricionais , Glicina , Deficiência Intelectual Ligada ao Cromossomo X , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores , Humanos , Feminino , Creatina/metabolismo , Creatina/deficiência , Glicina/metabolismo , Arginina/metabolismo , Arginina/uso terapêutico , Deficiência Intelectual Ligada ao Cromossomo X/genética , Deficiência Intelectual Ligada ao Cromossomo X/tratamento farmacológico , Deficiência Intelectual Ligada ao Cromossomo X/metabolismo , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/deficiência , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/genética , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/metabolismo , Encéfalo/metabolismo , Adulto , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Espectroscopia de Ressonância Magnética , Deficiência Intelectual/genética , Deficiência Intelectual/metabolismo , Deficiência Intelectual/tratamento farmacológico , Encefalopatias Metabólicas Congênitas , Proteínas de Membrana TransportadorasRESUMO
Pathogenic variants in SLC6A8, the gene which encodes creatine transporter SLC6A8, prevent creatine uptake in the brain and result in a variable degree of intellectual disability, behavioral disorders (e.g., autism spectrum disorder), epilepsy, and severe speech and language delay. There are no treatments to improve neurodevelopmental outcomes for creatine transporter deficiency (CTD). In this spotlight, we summarize recent advances in innovative molecules to treat CTD, with a focus on dodecyl creatine ester, the most promising drug candidate.