Dystonia 9

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The SLC2A1 gene at 1p34.2 codes for the 492 amino acid solute carrier family 2, facilitated glucose transporter member 1. This facilitative aldose transporter can transport a wide range of pentose and hexose sugars including glucose where it may be responsible for constitutive or basal cellular uptake. It is regulated by fibroblast growth factor 21. It has strong binary interactions with PDZ domain-containing protein GIPC1 and is complexed with beta-adducin, dematin and another solute carrier family 2, facilitated glucose transporter member 1 in a functional membrane complex.

Overexpression of SLC2A1 is associated with poor prognosis in solid human tumours[1].

Mutations of SLC2A1 cause:

  1. GLUT1 deficiency syndrome 1 (GLUT1DS1, OMIM:606777) which can present with a wise range of neurologic phenotypes. The most severe 'classic' form has infantile-onset epileptic encephalopathy within the first 4 months of life associated with delayed development, acquired microcephaly, motor incoordination, and spasticity. The seizures can have apnoeic episodes, staring spells, and episodic eye movements. There can be intermittent ataxia, confusion, lethargy, sleep disturbance, and headache. In other forms cognitive impairment varies from learning disabilities to severe mental retardation.
  2. GLUT1 deficiency syndrome 2 (GLUT1DS2, OMIM:612126) presenting usually with childhood onset paroxysmal exercise-induced dyskinesia, either transient dystonia or choreoathetosis. Childhood absence epilepsy and mild mental retardation may also occur. [2] Some have a macrocytic haemolytic anaemia.
  3. Idiopathic generalized epilepsy 12 (EIG12, OMIM:614847) which has recurrant generalized seizures including juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. In some patients the seizures may remit with age.
  4. Dystonia 9 (DYT9, OMIM:601042) which is an autosomal dominant disorder with childhood onset of paroxysmal choreoathetosis and progressive spastic paraplegia. Most patients show some degree of cognitive impairment and some can have seizures, migraine headaches, and ataxia.
  5. Stomatin-deficient cryohydrocytosis with neurologic defects (SDCHCN, OMIM:608885) with stomatocytosis characterized by episodic haemolytic anaemia, cold-induced red cells cation leak, erratic hyperkalaemia, neonatal hyperbilirubinemia, hepatosplenomegaly, cataracts, seizures, mental retardation, and movement disorders.