Asparagine Synthetase Deficiency

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Asparagine Synthetase Deficiency (ASNS) is caused by mutations (changes) in a gene called ASNS. This gene is responsible for providing instructions to make an enzyme called asparagine synthetase. The asparagine synthetase enzyme is found in cells throughout our bodies and converts a protein called aspartic acid to an amino acid called asparagine.  

Asparagine is used by our bodies to break down toxic ammonia within our cells. It is needed to make molecules that send out signals in the brain (neurotransmitter). Errors or changes in the ASNS gene result in a decrease or loss of asparagine synthetase enzymes, which impacts normal brain development. Asparagine can be found in our diets, however it cannot cross the blood-brain barrier, as this only allows for certain substances to pass between blood vessels and the brain.  

This is a very rare inherited condition. It is estimated that a total of 20 cases have been reported worldwide.  

This disorder causes neurological problems, usually apparent soon after birth. Most patients with this condition have an unusually small head size (otherwise known as microcephaly) that reduces over time due to loss of brain tissue. Other symptoms may include:

• Severe developmental delays affecting mental and motor skills. Typically, babies/infants cannot sit, crawl, walk or communicate verbally or nonverbally. Children who have achieved these milestones, sadly lose these skills over time.  
• Exaggerated reflexes and weak muscle tone.  
• Muscle stiffness, uncontrolled movements and eventually paralysis of the arms and legs.  
• Recurrent seizures  
• An exaggerated startle reaction 
• Loss of vision 

Sadly, children with Asparagine synthetase deficiency typically do not survive past childhood. 

This disorder is typically diagnosed via symptom review and genetic testing. A specialist or paediatrician will refer your child for genetic testing and these tests will look for mutations in the ASNS gene. After a diagnosis has been made, the following tests are usually conducted.  

•  A brain MRI to determine the extent of the condition  
• A review of frequency and type of seizures  
• An assessment for feeding problems  
• A musculoskeletal evaluation  
• A developmental assessment to evaluate and monitor speech and language and motor skills.  

There is currently no cure for this condition and the condition is usually managed by a multidisciplinary team in a supportive capacity. 

Asparagine Synthetase Deficiency is an inherited condition. Humans have chromosomes made up of DNA. Genes are pieces of DNA that carry the genetic information. Each chromosome may have several thousand genes. We inherit chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.  

 The pattern of inheritance of Asparagine Synthetase deficiency is autosomal recessive. This means that carriers of the condition do not have the disorder because the other gene of this pair is working normally. Parents of children with ASNS deficiency are carriers.   

When both parents are carriers, the risk to the baby in each pregnancy is  

• 25% chance (1 in 4) of developing the condition  
•  50% chance (1 in 2) for the baby to be a carrier of the condition  
•  25% chance (1 in 4) for the baby to have two working genes and neither have the condition nor be a carrier  

 Genetic counselling can be requested to get a full explanation.  

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing contact@metabolicsupportuk.org