GM3 Synthase Deficiency
What else is it called?
- Amish infantile epilepsy syndrome
- Epilepsy syndrome, infantile-onset symptomatic
- Ganglioside GM3 synthase deficiency
- Infantile-onset symptomatic epilepsy syndrome
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What causes it?
This disorder is caused by a fault in the ST3GAL5 gene which provides the instructions to allow our body to make an enzyme called GM3 Synthase. This enzyme is needed to produce a type of fat molecule called GM3 ganglioside which is important for brain function and development. A faulty gene means that not enough enzyme is produced and this leads to the signs and symptoms of this disorder, although it is unclear how the enzyme deficiency causes many of the signs and symptoms.
How common is it?
We do not know exactly how common this disorder is. However, researchers have recently combined information from natural history data of 104 individuals of Amish ancestry born between 1986 and 2017 with a definite or probable diagnosis.
What are the signs and symptoms?
Symptoms typically begin between 2 weeks and 3 months of age and may include:
- Muscle weakness
- Poor feeding/feeding difficulties requiring assistance via feeding tube.
- Failure to grow and gain weight at the expected rate (failure to thrive)
Seizures begin in the first year of life, becoming progressively worse and in some a cases, they may be prolonged (nonconvulsive status epilepticus). Seizures are often resistant to standard anti-epileptic medications.
Following the onset of seizures, symptoms affecting the brain begin to arise and children are likely to have severe intellectual disability and severe delays in reaching developmental milestones such as crawling, walking, and talking. Involuntary arm movements (choreoathetosis), weakness of the limbs (quadriparesis) and hearing and visual impairment develops slowly. Some children may also have distinctive facial features.
There may be differences in skin pigmentation which include dark freckle-like patches and lighter patches (hypopigmentation on the arms, legs, and face).
How is it diagnosed?
Diagnosis is based on a clinical examination and a range of specialised tests. It is often diagnosed shortly after birth. Genetic testing can confirm diagnosis.
Can it be treated?
Treatment is currently based on providing relief for the individual symptoms and support for the whole family. Research is on-going into potential treatment options for this condition. We do not know the prognosis for GM3 Synthase Deficiency.
Do my family need to be tested?
This disorder can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier.
If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have.
If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.
Once you receive a diagnosis, you can speak to a genetic counsellor. They can provide further information about inheritance and can also tell you about genetic testing for the rest of your family.