salt and pepper mental retardation syndrome

GM3 Synthase Deficiency

Clinical Characteristics
Ocular Features: 

Optic atrophy is the primary ocular feature in this disorder.  ERG amplitudes and retinal pigmentation are normal.  Visual impairment is pronounced with no reactions to threatening visual stimuli.  Eye movements are random and uncoordinated.  Optic atrophy is present but no retinal abnormalities have been reported.

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.

Hypo- and hyperpigmented skin macules in a 'salt and pepper' pattern, have been described.  These vary from 2-5 mm in size and are located primarily on the extremities.  These are found among children older than 3 years of age and some parents have reported that the hyperpigmentation may decrease after many years.  No such lesions were found in mucosal tissue.        

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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