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Disease Profile

GM3 synthase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Infantile-onset symptomatic epilepsy syndrome developmental stagnation blindness; Epilepsy syndrome, infantile-onset symptomatic; Amish infantile epilepsy syndrome;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases;

Summary

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]

Symptoms

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.

Medical Terms Other Names
Learn More:
HPO ID
5%-29% of people have these symptoms
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
Percent of people who have these symptoms is not available through HPO
Absent speech
Absent speech development
Lack of language development
Lack of speech
No speech development
No speech or language development
Nonverbal

[ more ]

0001344
Autosomal recessive inheritance
0000007
Bilateral tonic-clonic seizure
Grand mal seizures
0002069
Cerebral visual impairment
0100704
Choreoathetosis
0001266
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Developmental stagnation at onset of seizures
0006834
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
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
Hypermelanotic macule
Hyperpigmented spots
0001034
Hyporeflexia of upper limbs
0012391
Irritability
Irritable
0000737
Lower limb hyperreflexia
Overactive lower leg reflex
0002395
Multifocal epileptiform discharges
0010841
Muscular hypotonia
Low or weak muscle tone
0001252
Myoclonus
0001336
Optic atrophy
0000648
Status epilepticus
Repeated seizures without recovery between them
0002133
Visual loss
Loss of vision
Vision loss

[ more ]

0000572
Vomiting
Throwing up
0002013

Organizations

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

    Learn more

    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.

        References

        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. https://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; https://www.omim.org/entry/609056#5.