Creatine Transporter Deficiency Presenting as Failure to Thrive: A Case Report of a Novel <i>SLC6A8</i> Variant Causing a Treatable but Likely Underdiagnosed Genetic Disorder

Tise, Christina G.; Palma, Melinda J.; Cusmano‐Ozog, Kristina; Matalon, Dena

doi:10.1177/23247096231154438

Cited by 2 publications

(1 citation statement)

References 18 publications

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“…For example, creatine ( Box 1 ) is synthesised in the liver and kidneys ( da Silva et al, 2009 ) but is mostly utilised in cell types with high energy demand, such as skeletal muscle and neuronal cells ( Bessman and Geiger, 1981 ; Kazak and Cohen, 2020 ). The functioning of these cells, therefore, depends on the creatine transporter SLC6A8 (also known as CRT1), and reduced function of this transporter leads to symptoms such as intellectual disability and seizures ( Cervera-Acedo et al, 2015 ; Tise et al, 2023 ).…”

Section: Structure Function and Physiological Roles Of Membrane Trans...mentioning

confidence: 99%

Membrane transporters in cell physiology, cancer metabolism and drug response

Alam,

Doherty,

Ortega-Prieto

et al. 2023

Disease Models &Amp; Mechanisms

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By controlling the passage of small molecules across lipid bilayers, membrane transporters influence not only the uptake and efflux of nutrients, but also the metabolic state of the cell. With more than 450 members, the Solute Carriers (SLCs) are the largest transporter super-family, clustering into families with different substrate specificities and regulatory properties. Cells of different types are, therefore, able to tailor their transporter expression signatures depending on their metabolic requirements, and the physiological importance of these proteins is illustrated by their mis-regulation in a number of disease states. In cancer, transporter expression is heterogeneous, and the SLC family has been shown to facilitate the accumulation of biomass, influence redox homeostasis, and also mediate metabolic crosstalk with other cell types within the tumour microenvironment. This Review explores the roles of membrane transporters in physiological and malignant settings, and how these roles can affect drug response, through either indirect modulation of sensitivity or the direct transport of small-molecule therapeutic compounds into cells.

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Section: Structure Function and Physiological Roles Of Membrane Trans...mentioning

confidence: 99%

Membrane transporters in cell physiology, cancer metabolism and drug response

Alam,

Doherty,

Ortega-Prieto

et al. 2023

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

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Establishing a Core Outcome Set for Creatine Transporter Deficiency and Guanidinoacetate Methyltransferase Deficiency

Nasseri Moghaddam,

Reinhardt,

Thurm

et al. 2024

Preprint

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SUMMARYCreatine transporter (CTD) and guanidinoacetate methyltransferase (GAMT) deficiencies are rare inborn errors of creatine metabolism, resulting in cerebral creatine deficiency. Patients commonly exhibit intellectual and developmental disabilities, often accompanied by behavior problems, delayed speech, seizures, and motor impairments. There is currently no efficacious treatment for CTD, while the current management for GAMT requires lifelong treatment with a protein restricted diet and intake of high amounts of oral supplements. Efforts to develop effective, sustainable treatments for these disorders are limited by the lack of clinical and patient-derived meaningful outcomes. A core outcome set (COS) can facilitate consensus about outcomes for inclusion in studies. Unfortunately, patient and caregiver perspectives have historically been overlooked in the COS development process, thus limiting their input into the outcome selection. We partnered with caregivers and health professionals to establish the first COS for CTD and GAMT. The COS developed includes seven outcomes (“Adaptive Functioning”, “Cognitive Functioning”, “Emotional Dysregulation”, “MRS Brain Creatine”, “Seizure/Convulsions”, “Expressive Communication”, and “Fine Motor Functions”) for both CTD and GAMT, and an additional outcome for GAMT (“Serum/Plasma Guanidinoacetate”) that are important to stakeholders and consequently should be considered for measurement in every clinical trial. Caregivers were valued partners throughout the COS development process, which increased community engagement and facilitated caregiver empowerment. We expect this COS will ensure a patient-centered approach for accelerating drug development for CTD and GAMT, make clinical trial results comparable, minimize bias in clinical trial outcome selection, and promote efficient use of resources.1-sentence take home messageA core outcome set for creatine transporter (CTD) and guanidinoacetate methyltransferase (GAMT) deficiencies was created through a multiphase process in partnership with caregivers and health professionals.

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Creatine Transporter Deficiency Presenting as Failure to Thrive: A Case Report of a Novel SLC6A8 Variant Causing a Treatable but Likely Underdiagnosed Genetic Disorder

Cited by 2 publications

References 18 publications

Membrane transporters in cell physiology, cancer metabolism and drug response

Membrane transporters in cell physiology, cancer metabolism and drug response

Establishing a Core Outcome Set for Creatine Transporter Deficiency and Guanidinoacetate Methyltransferase Deficiency

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