GM3 synthase deficiency

GM3 synthase deficiency is characterized by recurrent seizures (epilepsy) and problems with brain development. Within the first few weeks after birth, affected infants become irritable and develop feeding difficulties and vomiting that prevent them from growing and gaining weight at the usual rate. Seizures begin within the first year of life and worsen over time. Multiple types of seizures are possible, including generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Some affected children also experience prolonged episodes of seizure activity called nonconvulsive status epilepticus. The seizures associated with GM3 synthase deficiency tend to be resistant (refractory) to treatment with antiseizure medications.

GM3 synthase deficiency profoundly disrupts brain development. Most affected children have severe intellectual disability and do not develop skills such as reaching for objects, speaking, sitting without support, or walking. Some have involuntary twisting or jerking movements of the arms that are described as choreoathetoid. Although affected infants can likely see and hear at birth, vision and hearing become impaired as the disease worsens. It is unknown how long people with GM3 synthase deficiency usually survive.

Some affected individuals have changes in skin coloring (pigmentation), including dark freckle-like spots on the arms and legs and light patches on the arms, legs, and face. These changes appear in childhood and may become more or less apparent over time. The skin changes do not cause any symptoms, but they can help doctors diagnose GM3 synthase deficiency in children who also have seizures and delayed development.