X-linked creatine transporter (SLC6A8) deficiency in females: Difficult to recognize, but a potentially treatable disease.

Autor: Mejdahl Nielsen M; Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: malene.mejdahl.nielsen.01@regionh.dk., Petersen ET; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark; Section for Magnetic Resonance, Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark., Fenger CD; Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Centre, Denmark; Amplexa Genetics, Odense, Denmark., Ørngreen MC; Center for Inherited Metabolic Diseases, Departments of Pediatrics and Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN) - Project ID No 739543, Denmark., Siebner HR; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark; Department of Neurology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Boer VO; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark., Považan M; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark., Lund A; Center for Inherited Metabolic Diseases, Departments of Pediatrics and Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN) - Project ID No 739543, Denmark., Grønborg SW; Center for Inherited Metabolic Diseases, Departments of Pediatrics and Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN) - Project ID No 739543, Denmark., Hammer TB; Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Centre, Denmark.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2023 Nov; Vol. 140 (3), pp. 107694. Date of Electronic Publication: 2023 Aug 30.
DOI: 10.1016/j.ymgme.2023.107694
Abstrakt: Creatine transporter deficiency (CTD), caused by pathogenic variants in SLC6A8, is the second most common cause of X-linked intellectual disability. Symptoms include intellectual disability, epilepsy, and behavioral disorders and are caused by reduced cerebral creatine levels. Targeted treatment with oral supplementation is available, however the treatment efficacy is still being investigated. There are clinical and theoretical indications that heterozygous females with CTD respond better to supplementation treatment than hemizygous males. Unfortunately, heterozygous females with CTD often have more subtle and uncharacteristic clinical and biochemical phenotypes, rendering diagnosis more difficult. We report a new female case who presented with learning disabilities and seizures. After determining the diagnosis with molecular genetic testing confirmed by proton magnetic resonance spectroscopy ( 1 H-MRS), the patient was treated with supplementation treatment including creatine, arginine, and glycine. After 28 months of treatment, the patient showed prominent clinical improvement and increased creatine levels in the brain. Furthermore, we provide a review of the 32 female cases reported in the current literature including a description of phenotypes, genotypes, diagnostic approaches, and effects of supplementation treatment. Based on this, we find that supplementation treatment should be tested in heterozygous female patients with CTD, and a prospective treatment underlines the importance of diagnosing these patients. The diagnosis should be suspected in a broad clinical spectrum of female patients and can only be made by molecular genetic testing. 1 H-MRS of cerebral creatine levels is essential for establishing the diagnosis in females, and especially valuable when assessing variants of unknown significance.
Competing Interests: Declaration of Competing Interest Hartwig R. Siebner has received honoraria as speaker from Sanofi Genzyme, Denmark, Lundbeck A/S, Denmark, and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark, Lophora, Denmark, and Lundbeck A/S, Denmark, and as editor-in-chief (Neuroimage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany and from Gyldendal Publishers, Copenhagen, Denmark.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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