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Genetics Home Reference: GM3 synthase deficiency

08/05/2014 11:30 PM EDT

Source: National Library of Medicine - NIH

GM3 synthase deficiency

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Reviewed July 2014

What is GM3 synthase deficiency?

GM3 synthase deficiency is characterized by recurrent seizures (epilepsy) and problems with brain development. Within the first few weeks after birth, affected infants become irritable and develop feeding difficulties and vomiting that prevent them from growing and gaining weight at the usual rate. Seizures begin within the first year of life and worsen over time. Multiple types of seizures are possible, including generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Some affected children also experience prolonged episodes of seizure activity called nonconvulsive status epilepticus. The seizures associated with GM3 synthase deficiency tend to be resistant (refractory) to treatment with antiseizure medications.

GM3 synthase deficiency profoundly disrupts brain development. Most affected children have severe intellectual disability and do not develop skills such as reaching for objects, speaking, sitting without support, or walking. Some have involuntary twisting or jerking movements of the arms that are described as choreoathetoid. Although affected infants can likely see and hear at birth, vision and hearing become impaired as the disease worsens. It is unknown how long people with GM3 synthase deficiency usually survive.

Some affected individuals have changes in skin coloring (pigmentation), including dark freckle-like spots on the arms and legs and light patches on the arms, legs, and face. These changes appear in childhood and may become more or less apparent over time. The skin changes do not cause any symptoms, but they can help doctors diagnose GM3 synthase deficiency in children who also have seizures and delayed development.

How common is GM3 synthase deficiency?

GM3 synthase deficiency appears to be a rare condition. About 50 cases have been reported, mostly from Old Order Amish communities.

What genes are related to GM3 synthase deficiency?

Mutations in the ST3GAL5 gene have been found to cause GM3 synthase deficiency. This gene provides instructions for making an enzyme called GM3 synthase, which carries out a chemical reaction that is the first step in the production of molecules called gangliosides. These molecules are present in cells and tissues throughout the body, and they are particularly abundant in the nervous system. Although their exact functions are unclear, gangliosides appear to be important for normal brain development and function.

ST3GAL5 gene mutations prevent the production of any functional GM3 synthase. Without this enzyme, cells cannot produce gangliosides normally. It is unclear how a loss of this enzyme leads to the signs and symptoms of GM3 synthase deficiency. Researchers are working to determine whether it is the lack of gangliosides or a buildup of compounds used to make gangliosides, or both, that underlies the seizures and other problems with brain development that occur in this condition. The connection between a shortage of GM3 synthase and changes in skin pigmentation is also unknown.

How do people inherit GM3 synthase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of GM3 synthase deficiency?

These resources address the diagnosis or management of GM3 synthase deficiency and may include treatment providers.

You might also find information on the diagnosis or management of GM3 synthase deficiency inEducational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about GM3 synthase deficiency?

You may find the following resources about GM3 synthase deficiency helpful. These materials are written for the general public.

MedlinePlus - Health information (4 links)
Additional NIH Resources - National Institutes of Health (2 links)
Educational resources - Information pages (5 links)
Patient support - For patients and families (4 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information (1 link)
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for GM3 synthase deficiency?

Amish infantile epilepsy syndrome
epilepsy syndrome, infantile-onset symptomatic
ganglioside GM3 synthase deficiency
ganglioside GM3 synthase deficiency
infantile-onset symptomatic epilepsy syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about GM3 synthase deficiency?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding GM3 synthase deficiency?

autosomal ; autosomal recessive ; cell ; deficiency ; disability ; enzyme ; epilepsy ; gene ; inherited ;involuntary ; mitochondria ; nervous system ; pigmentation ; recessive ; respiratory ; seizure ;skin pigmentation ; status epilepticus ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (4 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.