Related Experiment Video
Updated: May 30, 2026
10:41
Implantation of Osmotic Pumps and Induction of Stress to Establish a Symptomatic, Pharmacological Mouse Model for DYT/PARK-ATP1A3 Dystonia
Published on: September 12, 2020
Paroxysmal choreoathetosis/spasticity (DYT9) is caused by a GLUT1 defect.
1Departments of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Neurology
|August 12, 2011
Summary
Mutations in SLC2A1 cause glucose transporter type 1 (GLUT1) deficiency disorders. This study confirms GLUT1 mutations cause paroxysmal exercise-induced dyskinesia (PED) and progressive spastic paraparesis, expanding the known GLUT1 phenotypes.
Area of Science:
- Neurogenetics
- Molecular Neurology
Background:
- Mutations in SLC2A1, encoding the glucose transporter type 1 (GLUT1), are associated with various neurological disorders, including GLUT1 deficiency syndrome, paroxysmal exercise-induced dyskinesia (PED, DYT18), and absence epilepsy.
- A German/Dutch family with paroxysmal choreoathetosis/spasticity (DYT9) was previously linked to chromosome 1p, near but not including the SLC2A1 locus.
Observation:
- This study investigated the genetic basis of DYT9 and autosomal dominant hereditary spastic paraparesis (HSP) without PED.
- The German/Dutch family and an Australian twin pair with suspected GLUT1-related disorders were clinically re-evaluated.
- SLC2A1 sequencing was performed on these cases and 139 additional index patients with HSP.
Findings:
- Causative mutations in SLC2A1 were identified in the families with DYT9 and PED, demonstrating allelism between DYT9 and DYT18.
- These identified mutations impaired glucose uptake and protein expression in functional assays.
- SLC2A1 mutations were not found to cause HSP in patients without paroxysmal dyskinesias in the studied cohort.
Implications:
- This research expands the phenotypic spectrum of GLUT1 deficiency disorders to include slowly progressive spastic paraparesis combined with PED.
- It clarifies that DYT9 and DYT18 are allelic disorders.
- It excludes SLC2A1 mutations as a cause for HSP without PED in the investigated patient group.
Related Concept Videos
01:12Alterations in Muscle Tone ll
Alterations in muscle tone are common manifestations of neurological disorders and reflect dysfunction within different nervous system regions. Spasticity, paratonia, and dystonia represent distinct forms of hypertonia, each with unique mechanisms, clinical features, and diagnostic importance.CharacteristicsSpasticity happens from upper motor neuron lesions and is characterized by velocity-dependent resistance to passive movement. Clinical features include:Exaggerated deep tendon reflexesClonus...
01:21Huntington Disease l: Introduction
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
01:29Tetanus
Tetanus is a life-threatening neurological disorder characterized by persistent muscle contractions and spastic paralysis. It is caused by Clostridium tetani, a motile, Gram-positive, rod-shaped, obligate anaerobe. These bacteria produce terminal endospores, giving them a distinctive “lollipop” or “tennis-racket” appearance. They thrive in anaerobic environments, such as those found in deep puncture wounds.Once introduced into the body, the spores germinate into vegetative cells. These cells...
01:11Alterations in Muscle Tone lll
Rigidity and myotonia are distinct abnormalities of muscle tone that affect resistance and relaxation during movement. Although both involve altered muscle contraction, they arise from different neurological and muscular mechanisms.CharacteristicsRigidity is characterized by uniform resistance to passive movement across the entire range, independent of speed, affecting flexors and extensors equally. It may appear as lead-pipe rigidity (smooth, constant resistance) or cogwheel rigidity...
01:20Inborn Errors of Metabolism
Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
01:21Satellite Stem Cells and Muscular Dystrophy
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...