SIAT9

GM3 Synthase Deficiency

Clinical Characteristics
Ocular Features: 

Profound optic atrophy is the primary ocular feature in this disorder.  ERG amplitudes are normal.  Visual impairment is pronounced with no reactions to environmental stimuli but it is not possible to determine how much of this is due to general CNS disease.  Eye movements are random and uncoordinated. 

Systemic Features: 

Infants may appear normal at birth but within a few months develop signs of developmental stagnation with onset of tonic-clonic seizures.  Irritability, poor feeding, vomiting and failure to thrive are important features.  Generalized hypotonia is evident but lower limb deep tendon reflexes may be present.  Normal developmental milestones are never achieved and patients are unresponsive to their environment.  Older individuals develop non-purposeful choreothetoid movements.  The EEG shows multifocal epileptiform discharges and brain MRIs show diffuse atrophy in older patients.         

Genetics

This is an autosomal recessive disorder secondary to homozygous mutations in (ST3GAL5) (2p11.2) encoding sialytransferase (SIAT9).

The nonsense mutation results in a deficiency of functional GM3 synthase important in the utilization of lactosylceramide necessary for the production of downstream gangliosides.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

There is no known treatment for the enzyme deficiency.  Seizures respond poorly to anti-epileptic medications.

References
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