Treatment of X-linked creatine transporter (SLC6A8) deficiency: systematic review of the literature and three new cases
Dunbar M, Jaggumantri S, Sargent M, Stockler-Ipsiroglu S, van Karnebeek CD
Molecular genetics and metabolism · 52 citas
Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- British Columbia's Children's Hospital Foundation
Según 1 financiador declarado.
Publicación
- Publicado
- 2014-05-29 · Mol Genet Metab · vol. 112 · número 4 · págs. 259–274
- Editorial
- Elsevier BV
- Citado
- 76 citas · más que el 68% de estudios similares · 1.2× el promedio de su campo
- Referencias
- 36 trabajos
- Acceso
- De pago
- Áreas de investigación
- Metabolism and Genetic Disorders · Amino Acid Enzymes and Metabolism · Lysosomal Storage Disorders Research
- Palabras clave
- creatine transporter deficiency, SLC6A8, creatine supplementation, L-arginine, glycine supplementation, intellectual disability, treatment response, early treatment initiation, cyclocreatine, seizures, 1H NMR, treatment monitoring, treatment safety, treatment effectiveness
- MeSH
- humans, brain diseases, metabolic, inborn, creatine, membrane transport proteins, magnetic resonance imaging, treatment outcome, adolescent, child, child, preschool, infant, female, male, plasma membrane neurotransmitter transport proteins, x-linked intellectual disability
5 autores
- Mary Dunbar🇨🇦BC Children's Hospital
- Sravan Jaggumantri🇨🇦University of British Columbia; BC Children's Hospital; Child and Family Research Institute; BC Children's Hospital Research Institute
- Michael A. Sargent🇨🇦BC Children's Hospital
- Sylvia Stöckler‐Ipsiroglu🇨🇦University of British Columbia; BC Children's Hospital; Child and Family Research Institute; BC Children's Hospital Research Institute
- Clara van Karnebeek🇨🇦 · autor de correspondenciaUniversity of British Columbia; BC Children's Hospital; Child and Family Research Institute; BC Children's Hospital Research Institute
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
Creatine transporter deficiency (CTD) is an X-linked inborn error of creatine metabolism characterized by reduced intra-cerebral creatine, developmental delay/intellectual disability, (ID), behavioral disturbance, seizures, and hypotonia in individuals harboring mutations in the SLC6A8 gene. Treatment for CTD includes supplementation with creatine, either alone or in combination with creatine precursors (arginine or glycine). Unlike other disorders of creatine metabolism, the efficacy of its treatment remains controversial.
Methods
We present our systematic literature review (2001-2013) comprising 7 publications (case series/reports), collectively describing 25 patients who met the inclusion criteria, and 3 additional cases treated at our institution. Definitions were established and extracted data analyzed for cognitive ability, psychiatric and behavioral disturbances, epilepsy, and cerebral proton magnetic resonance spectroscopy measurements at pre- and post-treatment.
Results
Treatment regimens varied among the 28 cases: 2 patients received creatine-monohydrate supplementation; 7 patients received L-arginine; 2 patients received creatine-monohydrate and L-arginine; and 17 patients received a combination of creatine-monohydrate, L-arginine and glycine. Median treatment duration was 34.6 months (range 3 months-5 years). Level of evidence was IV. A total of 10 patients (36%) demonstrated response to treatment, manifested by either an increase in cerebral creatine, or improved clinical parameters. Seven of the 28 patients had quantified pre- and post-treatment creatine, and it was significantly increased post-treatment. All of the patients with increased cerebral creatine also experienced clinical improvement. In addition, the majority of patients with clinical improvement had detectable cerebral creatine prior to treatment. 90% of the patients who improved were initiated on treatment before nine years of age.
Conclusions
Acknowledging the limitations of this systematic review, we conclude that a proportion of CTD patients show amenability to treatment-particularly milder cases with residual brain creatine, and therefore probable residual protein function. We propose systematic screening for CTD in patients with ID, to allow early initiation of treatment, which currently comprises oral creatine, arginine and/or glycine supplementation. Standardized monitoring for safety and evaluation of treatment effects are required in all patients. This study provides effectiveness on currently available treatment, which can be used to discern effectiveness of future interventions (e.g. cyclocreatine).
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