What is citrullinemia

This gene provides instructions for making an enzyme, argininosuccinate synthase 1, that is responsible for one step of the urea cycle.

Mutations in the ASS1 gene reduce the activity of the enzyme, which disrupts the urea cycle and prevents the body from processing nitrogen effectively. Excess nitrogen in the form of ammonia and other byproducts of the urea cycle accumulate in the bloodstream.

Ammonia is particularly toxic to the nervous system, which helps explain the neurologic symptoms such as lethargy, seizures, and ataxia that are often seen in type I citrullinemia. This gene provides instructions for making a protein called citrin. Within cells, citrin helps transport molecules used in the production and breakdown of simple sugars, the production of proteins, and the urea cycle. Molecules transported by citrin are also involved in making nucleotides , which are the building blocks of DNA and its chemical cousin, RNA.

Mutations in the SLC25A13 gene typically prevent cells from making any functional citrin, which inhibits the urea cycle and disrupts the production of proteins and nucleotides. The resulting buildup of ammonia and other toxic substances leads to the signs and symptoms of adult-onset type II citrullinemia. Because citrullinemia is caused by problems with the urea cycle, it belongs to a class of genetic diseases called urea cycle disorders. Both types of citrullinemia are inherited in an autosomal recessive pattern , which means both copies of the respective 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. Genetics Home Reference has merged with MedlinePlus. Learn more. The information on this site should not be used as a substitute for professional medical care or advice.

Contact a health care provider if you have questions about your health. From Genetics Home Reference. Description Citrullinemia is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. Frequency Type I citrullinemia is the most common form of the disorder, affecting about 1 in 57, people worldwide. Inheritance Both types of citrullinemia are inherited in an autosomal recessive pattern , which means both copies of the respective gene in each cell have mutations.

Citrullinemia, type I is an inherited genetic condition that prevents the body from removing ammonia properly. Ammonia is a waste product produced when the body breaks down protein. You need arginosuccinate synthase I for a process in your body called the urea cycle. The urea cycle helps remove ammonia from the body. In citrullinemia, type I, this enzyme is missing or is not made correctly. High levels of ammonia are very toxic to the body, especially the brain and nerves.

If untreated, damage to the brain and nerves leads to the signs and symptoms of the condition. In severe cases, this condition can lead to coma or death if not treated early. To learn more about this process, visit the Blood Spot Screening page. When the urea cycle is not working well, citrulline builds up.

Babies with high levels of citrulline might have citrullinemia, type I. Together, you will discuss next steps and follow-up plans. An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. To learn more about screening results, visit the Blood Spot Screening Results page. You should complete any recommended follow-up testing as soon as possible.

Babies with this condition can have serious health problems very soon after birth if they are not diagnosed and treated quickly.

False-positive newborn screening results for this condition are rare. However, screening samples collected too early before the baby is 24 hours old may affect the results of screening. Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your dietician 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.

Low-protein diet The most effective treatment for citrullinemia is a diet with low amounts of protein. Foods that are high in protein need to be avoided or strictly limited include:.

Eating foods high in protein can cause ammonia to build up, causing severe illnesses. Many vegetables and fruits have only small amounts of protein and can be eaten in carefully measured amounts. Your child still needs a certain amount of protein for normal growth and development. Any changes in the diet should be made under the guidance of a dietvician. Medical foods and formula There are medical foods such as special low-protein flours, pastas, and rice that are made especially for people with amino acid disorders.

Your baby may need to drink a special medical formula that contains the correct amount of amino acids and nutrients. Your metabolic doctor and dietician will decide whether your child needs this treatment. 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.

Any diet changes should be made under the guidance of a dietician. Medication There are certain medications that can help the body get rid of ammonia. These medications are taken by mouth or by tube feeding to prevent high ammonia levels. Your doctor will decide whether your child needs these medications, which ones, and how much to use. During episodes of high ammonia, children need to be treated in the hospital.

Medications to remove ammonia are often given by IV 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.

Dialysis is sometimes needed to remove ammonia from the blood. An amino acid called arginine is often given by mouth to help prevent ammonia build-up. Your doctor will tell you whether your child needs arginine This is one of 20 amino acids that make up protein. 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.

Do not use any supplements or medications without checking with your doctor. Blood tests Your child will have regular blood tests to measure ammonia and amino acid levels. Call your doctor at the start of any illness For some babies and children with citrullinemia, even minor illnesses can cause high ammonia levels. In order to prevent problems, call your doctor right away when your child has any of the following:. Symptoms of high ammonia often need to be treated in the hospital.

Liver transplant surgery is an optional treatment for people with citrullinemia. The ASS enzyme that causes citrullinemia is located in the liver. Because of this, some children with citrullinemia have had liver transplantation surgery removal of their liver and replacement with a donor liver to treat their citrullinemia symptoms. 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. However, successful liver transplantation has been reported to improve quality of life and prolong survival in some cases. Liver transplantation does not reverse neurologic problems if they have already occurred. With prompt and lifelong treatment, children with citrullinemia can often live healthy lives with typical growth and learning.

Early treatment can help prevent high ammonia levels which decreases the risk for brain damage. Even with treatment, some children still have episodes of high ammonia. This can result in brain damage. This can cause lifelong learning problems, intellectual disabilities, or spasticity. Genes tell the body to make various enzymes. Everyone has two copies of the ASS1 gene. 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. 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. In children with citrullinemia, neither of these genes works correctly. Children with citrullinemia inherit one non-working gene for the condition from each parent.

Parents of a child with citrullinemia rarely have the condition themselves. Instead, each parent has a single non-working ASS1 gene for citrullinemia. They are called carriers 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.

Carriers do not have the condition because their other ASS1 gene is working correctly.