AMINO ACID DISORDER
Disorder name: Argininosuccinic acid lyase deficiency
Acronym: ASAL deficiency
- What is ASAL deficiency?
- What causes ASAL deficiency?
- If ASAL deficiency is not treated, what problems occur?
- What is the treatment for ASAL deficiency?
- What happens when ASAL deficiency is treated?
- How is ASAL deficiency inherited?
- What causes the ASAL enzyme to be absent or not working correctly?
- Is genetic testing available?
- What other testing is available?
- Can you test during a future pregnancy?
- Can other members of the family have ASAL deficiency or be carriers?
- Can other family members be tested?
- How many people have ASAL deficiency?
- Does ASAL deficiency happen more often in a certain ethnic group?
- Does ASAL deficiency go by any other names?
- Where can I find more information?
This fact sheet contains general information about ASAL deficiency. Every child is different and some of these facts may not apply to your child specifically. Certain treatments may be recommended for some children but not others. All children with this condition should be followed by a metabolic doctor in addition to their primary doctor.
WHAT IS ASAL DEFICIENCY?
ASAL stands for “argininosuccinic acid lyase.” ASAL deficiency is one type of amino acid disorders. People with this condition cannot remove ammonia from the body. This is a waste product made when protein is broken down for the body to use. Ammonia is harmful to the body. It is usually changed to a harmless substance called “urea.” Urea is then removed from the body in the urine. People with urea cycle disorders cannot get rid of ammonia. If these conditions are not treated, ammonia can build up and cause serious health problems. is a harmful substance. It is made when protein and its building blocks, Amino acids are small molecules that make up proteins. There are over 100 different amino acids, but our body uses only 20 amino acids to make all of its proteins. Our genes determine the sequence of amino acids in a protein. This sequence determines what shape the protein takes, and what function that protein serves in the body., are broken down for use by the body.
|Amino Acid Disorder:
These are a group of rare inherited conditions. People with amino acid disorders cannot digest particular amino acids – the building blocks of protein. These amino acids, along with other toxic substances, build up in the body. This can cause serious effects on health, growth, and learning. are a group of rare Acquiring a trait from one’s parents. Most traits, such as eye color or hair color, are inherited from a parent through genes. conditions. They are caused by A molecule that helps chemical reactions take place. For example, enzymes in the stomach speed up the process of breaking down food. Each enzyme can participate in many chemical reactions without changing or being used up. that do not work properly. A molecule that makes up many parts of every cell in the body. Examples of proteins include hormones, enzymes, hair, and antibodies. Proteins are made up of 20 different types of individual units called amino acids. It is the order of these amino acids in a protein that determines what form and function a protein has. Each gene holds the instructions for making a single protein. is made up of smaller building blocks called amino acids. A number of different enzymes are needed to process these amino acids for use by the body. Because of missing or non-working enzymes, people with amino acid disorders cannot process certain amino acids. These amino acids, along with other toxic substances, then build up in the body and cause problems. The symptoms and treatment vary between different amino acid disorders. They can also vary from person to person with the same amino acid disorder. See the fact sheets for each specific amino acid disorder. Amino acid disorders are inherited in an autosomal recessive manner and affect both males and females.
WHAT CAUSES ASAL DEFICIENCY?
ASAL deficiency is one of a small number of conditions called “These are inherited conditions that cause ammonia to build up in the body. Ammonia is a harmful waste product made during the breakdown of protein and its amino acid building blocks.” (UCD).
ASAL deficiency is caused by problems with the enzyme “argininosuccinic acid lyase” (ASAL). In people with ASAL deficiency, the ASAL enzyme is either missing or not working properly. This enzyme’s job is to help remove ammonia from the body.
When the ASAL enzyme is not working, ammonia and other harmful substances build up in the blood and cause brain damage. If not treated, excess ammonia can cause death.
IF ASAL DEFICIENCY IS NOT TREATED, WHAT PROBLEMS OCCUR?
Normally, the body changes ammonia into a substance called “This is a harmless waste product made by the body. Its job is to get rid of ammonia, a harmful substance made when protein is broken down for use by the body. The kidneys flush urea from the body in the urine..” Urea is then safely removed in the urine. However, if ammonia is not changed to urea, it begins to build up in the blood, which can be very harmful. If ammonia levels remain high for too long, severe brain damage can occur.
The symptoms of ASAL deficiency and the age they start vary from person to person. There are two types of ASAL deficiency. In the most common type, the symptoms start shortly after birth. There is also a milder type in which symptoms begin in late infancy or early childhood.
ASAL deficiency in newborns
Infants are healthy at birth but quickly develop symptoms. Within a few days of life, babies have high levels of ammonia in their blood. Some of the first symptoms of high blood ammonia are:
- poor appetite
- excessive sleepiness or lack of energy
If not treated, high ammonia levels can cause:
- muscle weakness
- decreased or increased In order to hold our posture and control our movements, a certain amount of tension is needed in our muscles. This tension is called “muscle tone.” People with hypotonia have too little tension in their muscles and appear “floppy.” People with hypertonia have too much tension in their muscles and have problems with tight, rigid muscles and joints.
- breathing problems
- problems staying warm
- These are also called "convulsions" or "fits." During a seizure, a person loses consciousness and control of his or her muscles. It may also cause involuntary movements. Seizures can happen for many reasons. Some causes are metabolic disorders, a metabolic crisis, brain injury, and infection.
- swelling of the brain
- This is a sleep-like condition from which a person cannot be awakened. People in a coma are unconscious. A coma can be caused by many things. Two causes are untreated low blood sugar (hypoglycemia) and a metabolic crisis., and sometimes death
Other effects of ASAL deficiency can include:
- poor growth
- enlarged liver
- delays in learning or intellectual disabilities
Without treatment, many babies die within the first few weeks of life.
ASAL deficiency in childhood
In this milder type of ASAL deficiency, symptoms start later in infancy or childhood. Some common symptoms in children who are not treated are:
- poor growth
- dry, brittle hair
- This refers to children who are unusually overactive. These children have serious problems sitting still. They tend to fidget and run around much more than usual. Some children with hyperactivity need treatment. They may be helped by behavior treatment, medication or both of these therapies.
- behavior problems
- learning or intellectual disabilities
- avoidance of meat and other high protein foods
- enlarged liver
- small head size
- high blood pressure
- episodes of excess ammonia in the blood
Episodes of high blood ammonia often happen:
- after long periods of going without food
- during illness or infection
- after high-protein meals
In children, some of the first symptoms of high blood ammonia are:
- poor appetite
- intense headache
- extreme sleepiness or lack of energy
- slurred speech
- poor coordination and balance problems
If not treated, children with high blood ammonia levels can develop:
- breathing problems
- swelling of the brain
- coma, sometimes leading to death
Some people have very mild symptoms and are diagnosed with ASAL deficiency after their brother or sister is diagnosed.
WHAT IS THE TREATMENT FOR ASAL DEFICIENCY?
Your baby’s primary doctor will work with a This is a doctor or medical geneticist who has special training in diagnosing and treating metabolic disorders. They often work in university hospitals or large medical centers. and a dietician to care for your child.
Prompt treatment is needed to prevent the build-up of ammonia. You should start treatment as soon as you know your child has this condition.
The following are treatments often recommended for babies and children with ASAL deficiency:
1. Low-protein diet and/or special medical foods and formula
Most children need to eat a diet made up of very low-protein foods, special medical foods, and sometimes a special formula. Your This is a person with special training in food and nutrition. A registered dietician (RD) has met the necessary educational requirements and has passed a national examination. If your child has a metabolic disorder, it is important for you to work with a registered dietician. They help create healthy food plans for people with metabolic disorders or other special needs. will create a food plan that contains the right amount of protein, nutrients, and energy to keep your child healthy. The food plan should be continued throughout your child’s life.
The most effective treatment is a diet with low amounts of protein. Foods that are high in protein need to be avoided or strictly limited and include:
- milk, cheese, and other dairy products
- meat and poultry
- dried beans and legumes
- nuts and peanut butter
Eating foods high in protein can cause ammonia to build up in the blood, resulting in severe illness. Many vegetables and fruits have only small amounts of protein and can be eaten in carefully measured portions.
It is important not to remove all protein from your child’s diet. Your child still needs a certain amount of protein for normal growth and development. Your dietician will help you create the best food plan for your child.
Medical foods and formula
There are medical foods such as special low-protein flours, pastas, and rice made especially for people with amino acid disorders.
Your baby may be given a special formula that contains the correct amount of nutrients and amino acids. Your metabolic doctor and dietician will decide whether your child needs this formula. Some states offer help with payment for this special formula and others require private insurance to pay for the formula and other special medical foods.
Your child’s exact food plan will depend on many things such as his or her age, weight, and general health. Your dietician will fine-tune your child’s diet over time. Any diet changes should be made under the guidance of a dietician familiar with ASAL deficiency.
Most children with ASAL deficiency are given arginine supplements by mouth. This is one of 20 amino acids that make up protein. It is also known as “Arg.” Most of the arginine needed is made by the body. In most cases, it does not need to be eaten in the diet. Arginine can also be bought in pill form. Children with certain urea cycle disorders are often given arginine supplements. These supplements can help clear the body of ammonia. helps the body remove ammonia from the blood. Your doctor will tell you whether your child needs these supplements and how much to take.
There are other medications that can help prevent high ammonia levels. These can either be taken by mouth or by tube feedings. Your metabolic doctor will decide whether your child needs this type of medication.
During episodes of high blood ammonia, children need to be treated in the hospital. Medications to remove ammonia are often given by This is a small tube placed into a vein, usually in the hand or arm. Medications and nutrients can be given through this tube directly into the blood. IV’s are often used in the hospital to give fluids, glucose and medication over a long period of time.. Sometimes dialysis is needed to remove ammonia from the blood.
3. Blood tests
Your child will have regular blood tests to measure amino acid and ammonia levels. Your child’s diet and medication may need to be adjusted based on blood test results.
4. Call your doctor at the start of any illness
For some babies and children, even minor illnesses can lead to build up of ammonia. In order to prevent problems, call your doctor right away when your child has any of the following:
- loss of appetite
- low energy or extreme sleepiness
- infection or illness
- behavior or personality changes
- difficulty walking or balance problems
Symptoms of high ammonia often need to be treated in the hospital. Ask your metabolic doctor if you should carry a special travel letter with medical instructions for your child’s care.
5. Liver transplantation
Liver transplant surgery has been tried in some children with ASAL who do not respond to other treatments. Liver transplant in children with ASAL deficiency does not cure the underlying disease and is only done when necessary.
Liver transplant is a major surgical procedure and has some risks. Individuals who have had a liver transplant must take medication for the rest of their lives to prevent their body from rejecting the donor liver. Many factors must be considered before surgery and this option should be discussed thoroughly with your child’s doctors.
WHAT HAPPENS WHEN ASAL DEFICIENCY IS TREATED?
With prompt and lifelong treatment, children with ASAL deficiency may be able to live healthy lives with typical growth and learning. Early treatment can help prevent high ammonia levels which decreases the risk for brain damage and intellectual disabilities.
Even with treatment, some children still have episodes of high ammonia. This can result in brain damage and can cause lifelong learning problems, intellectual disabilities, or This is rigidity of the muscles and increased reflexes. It is caused by increased muscle tone. It results in abnormal tightness or stiffness of the muscles and joints..
WHAT CAUSES THE ASAL ENZYME TO BE ABSENT OR NOT WORKING CORRECTLY?
Genes tell the body how to make various enzymes. The ASL gene instructs the body to make the ASAL enzyme. When the ASL A segment of DNA that contains the instructions to make a specific protein (or part of a protein). Genes are contained on chromosomes. Chromosomes, and the genes on those chromosomes, are passed on from parent to child. Errors in the DNA that make up a gene are called variants and can lead to diseases. do not work correctly, the ASAL enzyme is not made correctly or is not made at all.
HOW IS ASAL DEFICIENCY INHERITED?
This condition is inherited in an autosomal recessive manner. It affects both boys and girls equally.
Everyone has two copies of the ASL gene that make the ASAL enzyme. In children with ASAL deficiency, neither of these genes works correctly. These children inherit one non-working ASL gene from each parent.
Parents of children with ASAL deficiency rarely have the condition themselves. Instead, each parent has a single non-working ASL gene. They are called A person who has one copy of a gene mutation for a particular autosomal recessive disorder (remember genes come in pairs). Carriers are not affected by the disorder. However, they can pass on the gene variant to their children. Children who inherit two such gene variants will be affected by the disorder. The term variants is now used in place of the term mutation.. Carriers do not have the condition because their other ASL gene is working correctly.
When both parents are carriers, there is a 25% chance in each pregnancy for the child to have ASAL deficiency. There is a 50% chance for the child to be a carrier, just like the parents. And, there is a 25% chance for the child to have two working genes.
Relating to (or due to) genes and heredity or the field of studying genes and heredity. counseling is available to families who have children with ASAL deficiency. Genetic counselors can answer your questions about how the condition is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a These are health care providers who have special training in genetic conditions. They help families understand genetic disorders and how they are passed down. Genetic counselors offer information and support to people who have genetic conditions in their families or are concerned that they may have a child with an inherited disorder..
IS GENETIC TESTING AVAILABLE?
Genetic testing for ASAL deficiency is available. Genetic testing, also called DNA testing, looks for changes called A variant is a change or alteration in a person’s DNA sequence. Variants can happen in genes and affect how the gene functions. There are different types of variants – they can be non-problem causing (benign), disease-causing (pathogenic) or of unknown significance. The term variants is now used in place of the term mutation., in the ASL genes. Ask your metabolic doctor or genetic counselor whether Deoxyribonucleic acid (DNA) is a molecule found in the chromosomes that carries genetic information. DNA is composed of four units (called bases) that are designated A, T, G, and C. The sequence of the bases spell out instructions for making all of the proteins needed by an organism. A gene is a section of DNA that holds the instructions for a specific protein. A change in one or more of the DNA bases making up a gene is called a mutation. Some mutations change the protein instructions and can lead to particular health problems or disorders. Each parent passes half of their chromosomes, and thus half of their DNA instructions, onto their children. It is these instructions that cause certain traits, such as eye or hair color, to be inherited. testing is available to your family.
DNA testing is not necessary to diagnose your child. It can be helpful for carrier testing or prenatal diagnosis, discussed below.
WHAT OTHER TESTING IS AVAILABLE?
Special tests on blood, urine, or skin samples can be done to confirm if your child has ASAL deficiency. Talk to your metabolic doctor or genetic counselor if you have questions about this type of testing.
CAN YOU TEST DURING A FUTURE PREGNANCY?
If both gene changes (variants) have been found in your child with ASAL deficiency, DNA testing can be done during future pregnancies. The sample needed for this test is obtained by either CVS or This is a test done during pregnancy. A needle is used to remove a small sample of fluid from the sac around the fetus. The sample can be used to test for certain genetic disorders in the fetus. Amniocentesis to test for genetic conditions is usually done between 13 and 20 weeks of pregnancy..
If DNA testing would not be helpful, an enzyme test can be done on The smallest living unit. Cells make up all organs and tissues in multi-cellular organisms, like humans. They can also live independently, as in bacteria and other microorganisms. At a minimum, a cell is surrounded by a membrane, contains DNA at some stage in its life, and is able to replicate itself into two equal parts. from the fetus. Again, the sample needed for this test is obtained by either This is a special test done early in pregnancy. During CVS, a small sample of the placenta is removed for testing. This sample can be used to test for certain genetic disorders in the fetus. CVS is usually done between 10 and 12 weeks of pregnancy. or amniocentesis.
Parents may choose to have testing during pregnancy or wait until birth to have the baby tested. Parents may also choose to use assisted reproductive techniques to decrease the chance that their future children would have ASAL deficiency. A genetic counselor can talk to you about your choices and answer questions about prenatal testing or testing your baby after birth.
CAN OTHER MEMBERS OF THE FAMILY HAVE ASAL DEFICIENCY OR BE CARRIERS?
Having ASAL deficiency
The brothers and sisters of a baby with ASAL deficiency have a small chance of being affected, even if they haven’t had symptoms. Finding out if other children in your family have this condition is important because early treatment can prevent serious health problems. Talk to your metabolic doctor or genetic counselor about testing your other children.
ASAL deficiency carriers
Brothers and sisters who do not have the condition have a chance to be carriers like their parents. Except in special cases, carrier testing should only be done in people over 18 years of age.
If you are a parent of a child with ASAL deficiency, your brothers and sisters have a 50% chance to be a carrier. It is important for other family members to be told that they could be carriers. There is a chance they are also at risk to have children with ASAL deficiency.
All states offer A screening test that looks for different disorders using a small sample of blood taken from a newborn’s heel. A positive or abnormal newborn screening result means that there are slight differences that were found in the baby’s blood, and further testing is needed to figure out if the baby has a metabolic disorder. for ASAL. However, when both parents are carriers, newborn The process of testing for disease in a person who does not show signs of having the disease (nonsymptomatic or asymptomatic person). The goal of screening is to catch the disease in its early stages. results are not sufficient to rule out the condition in a newborn baby. In this case, special diagnostic testing should be done in addition to newborn screening.
CAN OTHER FAMILY MEMBERS BE TESTED?
Brothers and sisters of a child with ASAL deficiency can be tested using blood, urine, or skin samples to see if they also have this disorder.
If both gene changes in the ASL genes have been found in your child, other family members can have DNA testing to see if they are carriers.
If the gene changes cannot be found, DNA testing would not be helpful for carrier testing. However, other methods of carrier testing may be available. Your metabolic doctor or genetic counselor can answer your questions about carrier testing.
HOW MANY PEOPLE HAVE ASAL DEFICIENCY?
This is a rare condition. About one in every 70,000 babies in the United States is born with ASAL deficiency.
DOES ASAL DEFICIENCY HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?
ASAL deficiency does not happen more often in any specific race, ethnic group, geographical area, or country.
DOES ASAL DEFICIENCY GO BY ANY OTHER NAMES?
ASAL deficiency is sometimes also called:
- Argininosuccinase deficiency
- Argininosuccinic aciduria
- Argininosuccinic acidemia
- Argininosuccinic acid lyase deficiency
- ASL deficiency
- Arginine succinate lyase deficiency
WHERE CAN I FIND MORE INFORMATION?
National Urea Cycle Disorders Foundation
Metabolic Support UK
Baby’s First Test
Urea Cycle Disorders Consortium Registry
|HI, CA, OR, and WA metabolic specialists
|September 31, 2007
September 31, 2010
May 20, 2013
March 9, 2020
March 1, 2023
|March 1, 2023
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