Biomarkers

Biomarkers

Biomarkers refer to medical signs or objective indications of a disease. There are multiple biomarkers associated with SLC13A5 Citrate Transporter Disorder that have been published and are currently under investigation. We have provided a general description of some biomarkers associated with SLC13A5 Citrate Transporter Disorder.

Citrate: SLC13A5 Citrate Transporter Disorder is caused by mutations in the Slc13a5 gene that code for a sodium citrate cotransporter, NaCT. NaCT is responsible for transporting citrate, a key substrate in cellular metabolism, from the extracellular fluid into the cell. Mutations in Slc13a5 lead to decreased expression, function, and mislocalization of NaCT. Consistent with this, patients with SLC13A5 Citrate Transporter Disorder have elevated citrate levels in the CSF, plasma, and urine (Bainbridge et al. 2017).

Electroencephalography (EEG): Patients with SLC13A5 Citrate Transporter Disorder start experiencing seizures within hours to days after birth. Despite frequent seizures, SLC13A5 Citrate Transporter Disorder patients have EEGs with relatively normal background for age (Matricardi et al. 2020, Yang et al. 2020). This contrasts with many other epileptic encephalopathies which have more disordered backgrounds.

Magnetic resonance imaging (MRI): Patients with SLC13A5 Citrate Transporter Disorder show minor abnormalities of punctate white matter lesions during the neonatal period that are no longer visible at 6 months of age (Weeke et al 2017).

Movement: A majority of patients have ataxia (loss of full control of bodily movements) and hypotonia (decreased muscle tone). The specific movement changes have yet to be characterized.

Teeth: Tooth abnormalities, including tooth hypoplasia or hypodontia, are reported in a majority of patients with SLC13A5 Citrate Transporter Disorder (Matricardi et al. 2020, Hardies et al. 2015). This is a common phenotype of channel mutants.