National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

GM3 synthase deficiency


Other Names:
Infantile-onset symptomatic epilepsy syndrome - developmental stagnation - blindness; Epilepsy syndrome, infantile-onset symptomatic; Amish infantile epilepsy syndrome; Infantile-onset symptomatic epilepsy syndrome - developmental stagnation - blindness; Epilepsy syndrome, infantile-onset symptomatic; Amish infantile epilepsy syndrome; ST3GAL5-CDG; Salt and pepper syndrome See More
Categories:
This disease is grouped under:
GM3 synthase deficiency is a rare neurological disorder in which the brain does not develop normally. Symptoms of the disease begin within the first weeks or months of life and include difficulty feeding, irritability, vomiting, and seizures accompanied by loss of consciousness (grand mal seizures). Vision and hearing loss, spots of darker skin color (hyperpigmentation), and intellectual and developmental delays develop as the disease progresses.[1] GM3 synthase deficiency is a congenital disorder of glycosylation and includes both cases described as Amish infantile epilepsy syndrome and cases described as salt & pepper syndrome.

GM3 synthase deficiency is caused by a mutation in the ST3GAL5 gene and is inherited in an autosomal recessive manner. The ST3GAL5 gene tells the body to make an enzyme that supports gangliosides, which are molecules that are important for brain development and function.[1][2][3]

GM3 synthase deficiency is suspected when a child presents with symptoms characteristic of the disease. Genetic testing confirms the diagnosis. Treatment is focused on relieving symptoms of the disease, which may include nutritional and feeding support and medications to lessen the severity of seizures. Although there is no cure for the condition, children with GM3 synthase deficiency have lived into early adulthood.[2][3]
Last updated: 8/3/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood
[ more ] 		0002376
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Intellectual disability, profound
IQ less than 20
0002187
Irritability
Irritable
0000737
Profound global developmental delay 0012736
Sensorineural hearing impairment 0000407
30%-79% of people have these symptoms
Absent speech
Absent speech development
Lack of language development
Lack of speech
No speech development
No speech or language development
Nonverbal
[ more ] 		0001344
Cerebral visual impairment 0100704
Gastrostomy tube feeding in infancy 0011471
Hypermelanotic macule
Hyperpigmented spots
0001034
Inability to walk 0002540
Increased serum lactate 0002151
Optic atrophy 0000648
Poor eye contact 0000817
Progressive neurologic deterioration
Worsening neurological symptoms
0002344
5%-29% of people have these symptoms
Abnormality of the cerebral white matter 0002500
Bilateral ptosis
Drooping of both upper eyelids
0001488
Bilateral tonic-clonic seizure
Grand mal seizures
0002069
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Depigmentation/hyperpigmentation of skin 0007483
Developmental stagnation 0007281
Gastrointestinal dysmotility 0002579
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Myoclonus 0001336
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Paroxysmal choreoathetosis 0007098
Status epilepticus
Repeated seizures without recovery between them
0002133
Stereotypy
Repetitive movements
Repetitive or self-injurious behavior
[ more ] 		0000733
Tetraparesis 0002273
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance 0000007
Choreoathetosis 0001266
Developmental stagnation at onset of seizures 0006834
Feeding difficulties in infancy 0008872
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Global brain atrophy
Generalized brain degeneration
0002283
Global developmental delay 0001263
Hyporeflexia of upper limbs 0012391
Lower limb hyperreflexia
Overactive lower leg reflex
0002395
Multifocal epileptiform discharges 0010841
Muscular hypotonia
Low or weak muscle tone
0001252
Visual loss
Loss of vision
Vision loss
[ more ] 		0000572
Vomiting
Throwing up
0002013
Showing of 44 |
Last updated: 7/1/2020

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Konstantina Fragaki, Samira Ait-El-Mkadem, Annabelle Chaussenot, Catherine Gire, Raymond Mengual, Laurent Bonesso, Marie Bénéteau, Jean-Ehrland Ricci, Valérie Desquiret-Dumas, Vincent Procaccio, Agnès Rötig and Véronique Paquis-Flucklinger. Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency. European Journal of Human Genetics; September 19, 2012; 21:528-534. http://www.nature.com/ejhg/journal/v21/n5/full/ejhg2012202a.html.
  2. GM3 syntase deficiency. Genetics Home Reference; July 2014; https://ghr.nlm.nih.gov/condition/gm3-synthase-deficiency.
  3. Cassandra L. Kniffin and Victor A. McKusick. Amish infantile epilepsy syndrome. Online Mendelian Inheritance in Man; July 15, 2014; http://www.omim.org/entry/609056#5.