SNP Shot: Genomic Insights

GM3 synthase deficiency is a condition marked by recurring seizures (epilepsy) and impaired brain development. Infants with this deficiency often exhibit irritability, feeding problems, and vomiting shortly after birth, hindering their growth and weight gain. Seizures typically start within the first year and progressively worsen. These seizures can manifest in various forms, including generalized tonic-clonic seizures (grand mal seizures), characterized by muscle stiffness, convulsions, and loss of consciousness. Some children may also experience prolonged seizure episodes known as nonconvulsive status epilepticus. Unfortunately, seizures linked to GM3 synthase deficiency are often difficult to control with standard antiseizure drugs.

Brain development is severely affected by GM3 synthase deficiency. Most children with this condition experience significant intellectual disability and struggle to acquire developmental milestones like reaching, speaking, sitting unsupported, or walking. Some may also display involuntary, twisting or jerking movements of the arms (choreoathetoid movements). While infants may initially have normal vision and hearing, these senses tend to deteriorate as the disease progresses. The life expectancy for individuals with GM3 synthase deficiency remains unknown.

Certain individuals with GM3 synthase deficiency exhibit alterations in skin pigmentation. These can include dark, freckle-like spots on the limbs and lighter patches on the arms, legs, and face. These skin changes usually appear during childhood and may fluctuate in prominence over time. While these changes are asymptomatic, they can be a valuable diagnostic clue for doctors in children presenting with seizures and developmental delays.

Inheritance:

GM3 synthase deficiency follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. The parents, who each carry only one copy of the mutated gene, typically do not exhibit any symptoms or signs of the deficiency themselves.