Episodic Ataxia, Type 6

Last update 08 May 2025

Basic Info

Synonyms

EA6, EPISODIC ATAXIA, TYPE 6, EPISODIC ATAXIA, TYPE 6 (disorder)

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Introduction

An exceedingly rare form of hereditary episodic ataxia with varying degrees of ataxia and associated findings including slurred speech, headache, confusion and hemiplegia.

Clinical Trials associated with Episodic Ataxia, Type 6

NCT01793168

/ RecruitingNot Applicable

Coordination of Rare Diseases at Sanford

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to enroll.

Start Date01 Jul 2010

Sponsor / Collaborator

Sanford Health Corp.

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100 Clinical Results associated with Episodic Ataxia, Type 6

100 Translational Medicine associated with Episodic Ataxia, Type 6

0 Patents (Medical) associated with Episodic Ataxia, Type 6

Literatures (Medical) associated with Episodic Ataxia, Type 6

01 Aug 2022·Current Opinion in Structural Biology

The twisting elevator mechanism of glutamate transporters reveals the structural basis for the dual transport-channel functions

Review

Author: Font, Josep ; Wu, Qianyi ; Ryan, Renae M ; Chen, Ichia

Glutamate transporters facilitate the removal of this excitatory neurotransmitter from the synapse. Increasing evidence indicates that this process is linked to intrinsic chloride channel activity that is thermodynamically uncoupled from substrate transport. A recent cryo-EM structure of Glt_Ph - an archaeal homolog of the glutamate transporters - in an open channel state has shed light on the structural basis for channel opening formed at the interface of two domains within the transporter which is gated by two clusters of hydrophobic residues. These transporters cycle through several conformational states during the transport process, including the chloride conducting state, which appears to be stabilised by protein-membrane interactions and membrane deformation. Several point mutations that perturb the chloride conductance can have detrimental effects and are linked to the pathogenesis of the neurological disorder, episodic ataxia type 6.

01 Dec 2021·Molecular Genetics and MetabolismQ2 · BIOLOGY

Reduction of glutamate neurotoxicity: A novel therapeutic approach for Niemann-Pick disease, type C1

Q2 · BIOLOGY

Article

Author: Wassif, Christopher A ; Yerger, Julia C ; Serra-Vinardell, Jenny ; Cougnoux, Antony ; Cawley, Niamh X ; Porter, Forbes D ; Navid, Fatemeh ; Fellmeth, Mason

Niemann-Pick disease, type C1 is a progressive, lethal, neurodegenerative disorder due to endolysosomal storage of unesterified cholesterol. Cerebellar ataxia, as a result of progressive loss of cerebellar Purkinje neurons, is a major symptom of Nieman-Pick disease, type C1. Comparing single cell RNAseq data from control (Npc1^+/+) and mutant (Npc1^-/-) mice, we observed significantly decreased expression of Slc1a3 in Npc1^-/- astrocytes. Slc1a3 encodes a glutamate transporter (GLAST, EAAT1) which functions to decrease glutamate concentrations in the post synaptic space after neuronal firing. Glutamate is an excitatory neurotransmitter and elevated extracellular levels of glutamate can be neurotoxic. Impaired EAAT1 function underlies type-6 episodic ataxia, a rare disorder with progressive cerebellar dysfunction, thus suggesting that impaired glutamate uptake in Niemann-Pick disease, type C1 could contribute to disease progression. We now show that decreased expression of Slc1a3 in Npc1^-/- mice has functional consequences that include decreased surface protein expression and decreased glutamate uptake by Npc1^-/- astrocytes. To test whether glutamate neurotoxicity plays a role in Niemann-Pick disease, type C1 progression, we treated NPC1 deficient mice with ceftriaxone and riluzole. Ceftriaxone is a β-lactam antibiotic that is known to upregulate the expression of Slc1a2, an alternative glial glutamate transporter. Although ceftriaxone increased Slc1a2 expression, we did not observe a treatment effect in NPC1 mutant mice. Riluzole is a glutamate receptor antagonist that inhibits postsynaptic glutamate receptor signaling and reduces the release of glutamate. We found that treatment with riluzole increased median survival in Npc1^-/- by 12%. Given that riluzole is an approved drug for the treatment of amyotrophic lateral sclerosis, repurposing of this drug may provide a novel therapeutic approach to decrease disease progression in Niemann-Pick disease type, C1 patients.

01 Nov 2020·Human MutationQ2 · MEDICINE

Functional consequences of SLC1A3 mutations associated with episodic ataxia 6

Q2 · MEDICINE

Article

Author: Fahlke, Christoph ; Kovermann, Peter ; Kortzak, Daniel ; Chivukula, Aparna S. ; Suslova, Mariia

The episodic ataxias (EA) are a group of inherited neurological diseases characterized by paroxysmal cerebellar incoordination. There exist nine forms of episodic ataxia with distinct neurological symptoms and genetic origins. Episodic ataxia type 6 (EA6) differs from other EA forms in long attack duration, epilepsy and absent myokymia, nystagmus, and tinnitus. It has been described in seven families, and mutations in SLC1A3, the gene encoding the glial glutamate transporter EAAT1, were reported in each family. How these mutations affect EAAT1 expression, subcellular localization, and function, and how such alterations result in the complex neurological phenotype of EA6 is insufficiently understood. We here compare the functional consequences of all currently known mutations by heterologous expression in mammalian cells, biochemistry, confocal imaging, and whole-cell patch clamp recordings of EAAT1 transport and anion currents. We observed impairments of multiple EAAT1 properties ranging from changes in transport function, impaired trafficking to increased protein expression. Many mutations caused only slight changes illustrating how sensitively the cerebellum reacts on impaired EAAT1 functions.

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Episodic Ataxia, Type 6

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