OMIM ID:
GM3 Synthase Deficiency
Alternate Names
Defective Genes
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
Inheritance
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
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.