SNP Shot: Genomic Insights

GLUT1 deficiency syndrome is a neurological disorder presenting with a range of signs and symptoms. The most common form, affecting about 90% of individuals, is often called common GLUT1 deficiency syndrome. These individuals typically experience frequent seizures (epilepsy) that start in early infancy. An early indicator in newborns can be rapid, involuntary eye movements. While babies with this form have a normal head size at birth, their brain and skull growth often slows, potentially leading to an abnormally small head (microcephaly). Developmental delays or intellectual disability are common in this group. Many also have other neurological issues such as muscle stiffness (spasticity), coordination problems (ataxia), and speech difficulties (dysarthria). Some may experience episodes of confusion, lethargy, headaches, or muscle twitches (myoclonus), especially during fasting.

Approximately 10% of individuals have a less severe form, often referred to as non-epileptic GLUT1 deficiency syndrome. Those with this form do not experience seizures but may still have developmental delays and intellectual disability. Movement problems, such as ataxia or involuntary muscle tensing (dystonia), are common and may be more pronounced compared to the common form.

Several conditions originally diagnosed under different names have since been identified as variants of GLUT1 deficiency syndrome. These include paroxysmal choreoathetosis with spasticity (dystonia 9), paroxysmal exercise-induced dyskinesia and epilepsy (dystonia 18), and specific types of epilepsy. In rare cases, individuals with these variants may have abnormal red blood cells, leading to uncommon forms of anemia (a shortage of red blood cells).

Inheritance:

The condition usually follows an autosomal dominant inheritance pattern, meaning only one copy of the mutated gene is needed to cause the disorder. About 90% of GLUT1 deficiency syndrome cases arise from new gene mutations, occurring in individuals with no family history of the condition. In other instances, the affected person inherits the mutated gene from an affected parent. Rarely, GLUT1 deficiency syndrome is inherited in an autosomal recessive pattern, requiring both copies of the gene to be mutated. In these cases, each parent carries one copy of the mutated gene but typically does not exhibit symptoms of the condition.