Argininemia

Argininemia is a genetic condition and there is no cure. A person will never outgrow the disorder. People with this disorder will have to be on a special diet and receive medications throughout their lives.

People with argininemia must follow a special, low-protein diet for their entire lives. This is because a certain building block of protein, called arginine, cannot be broken down in the bodies of people with argininemia. For this reason, it is important to avoid arginine and limit protein in the diet for a person’s entire life. People with argininemia must also eat special medical foods to help make up for nutrients that they miss getting because of their special diet. There are special medical foods created specifically for people with amino acid disorders. The National Urea Cycle Disorders Foundation has information on where to get special medical foods. Current guidelines strongly recommend that people with argininemia follow a special diet including using supplemental medical foods for their entire lives.

Some people with argininemia may choose to stop following their diet as they get older. This is called poor compliance. A low protein, arginine-restricted diet, is very restrictive and some people have trouble staying on the diet. Children, particularly older children, may stop following the diet because they are embarrassed or their classmates may make unkind comments. Children or teenagers who struggle with compliance should talk to their parents, physicians and a psychologist to work through these issues.

Sometimes people stop following the diet because it’s working well and they feel better. They may start to think that they do not need to follow the diet anymore or ‘cheat’ on the diet more and more often. However, the less they follow their diets, the more arginine and other compounds will keep building up in their bodies. The special diet to treat argininemia must be followed for life. Even if someone feels better and their symptoms improve, they need to continue to follow their treatment plan as developed by their physician and medical team in order to continue feeling better.

Parents and individuals should work closely with a metabolic dietitian in planning their diets. To find a metabolic dietitian specializing in diets for people with metabolic conditions, visit the GMDI Find a Metabolic Dietitian webpage.

In a family with argininemia, tests can be done to see whether other family members are carriers for the disorder. (Carriers do not have symptoms and have one working and one non-working copy of the ARG1 gene.) However, the specific gene changes in that family needs to be known. If known, all siblings and other at-risk relatives can be tested. Molecular genetic testing, which are tests that look for changes to genes, can be performed. A newborn child in a family with a history of argininemia should be tested through molecular genetic testing. A genetic counselor or a physician with experience in argininemia can provide advice about how a confirmed diagnosis can affect other family members. Medical geneticists can be found through the American College of Medical Genetics and a genetic counselor can be found through the National Society of Genetic Counselors.

Support groups are organizations that provide support, information, advice, referrals to physicians and medical centers, and up-to-date information on research and treatments. Support groups for argininemia include the National Urea Cycle Disorders Foundation. This organization represents all urea cycle disorders.

There are also online communities for rare disorders such as RareConnect, RareShare, or Inspire, which allow individuals and parents to share experiences and advice about dealing with rare disorders.

Taking care of someone with a long-term or chronic condition can be tiring and challenging and this is no different for parents or other caregivers of people with argininemia. If you are a caregiver in need of support, try to take time for yourself, set aside time for personal counseling, or look for other resources at the Caregiver Action Network. This organization works to improve the quality of life for people who care for loved ones with chronic conditions, disabilities, disease, or the frailties of old age. Support groups can also help provide support and advice for caregivers. Support groups for argininemia include, The National Urea Cycle Disorders Foundation.

According to the medical literature, there is evidence that early diagnosis and prompt treatment (before symptoms begin) can prevent the neurological problems associated with argininemia. There are reports of people who remained symptom-free when treated from birth, with the oldest person being more than 35 years old. If symptoms were already present when treatment was started, good results can still be achieved. This is true if treatment was started before significant problems have developed. The progression of neurological disease can be stopped and some skills can be reacquired. However, not all infants and children will respond to treatment and treatment cannot repair damage to the brain that has already occurred. Consequently, life expectancy will depend on several factors including when the disorder was first diagnosed and what symptoms had already developed. Also, argininemia can affect one person very differently from how it affects another person. It is difficult to make predictions about how the disorder will progress for an individual. Although less common, there are very severe forms of argininemia, which can be life-threatening early in life.

Talk to your doctors and entire medical team about your or your child’s diagnosis and individual situation. The National Urea Cycles Disorders Foundation provides information, support, advice and networking options for people with urea cycle disorders like argininemia.

Argininemia is a rare genetic disorder. People with argininemia have problems with an enzyme called arginase I as it is either missing, deficient, or damaged. The arginase I enzyme has an important job as part of the urea cycle and you may hear argininemia referred to as a urea cycle disorder. This cycle is series of biochemical reactions that occur in the body to help to break down (metabolize) and then remove excess nitrogen from the body. Nitrogen is obtained from the diet and is a normal waste product of the metabolism of protein. Nitrogen is broken down into a compound called urea that is excreted from the body in the urine. People with argininemia cannot properly break down the amino acid arginine, which is one of the steps of urea cycle. An amino acid is a building block of protein. Because they cannot break down arginine and cannot completely convert nitrogen into urea, arginine and nitrogen (in the form of ammonia) build up in the body.

Unlike most urea cycle disorders, argininemia usually does not cause severe symptoms in infancy. Infants may be irritable, vomit and exhibit feeding problems. They may be less alert when given cow’s milk. Some infants may refuse to eat. Argininemia will affect the central nervous system. If untreated, around the age or 3 or 4, children may be clumsy and may fail to gain weight or grow as would be normally expected. They may have delays in reaching developmental milestones and may lose skills that they had already developed. Seizures are common and intellectual disability, tremors, and a condition called spasticity also develop. Spasticity is when there is increased muscle tone and stiffness of leg muscles and can cause muscle spasms.

Unlike the other urea cycle disorders, infants and children with argininemia rarely have what is called a metabolic crisis due to elevated ammonia levels. Ammonia is a neurotoxin that damages central nervous system cells called neurons when there is too much ammonia in the body. In a serious metabolic crisis an infant may vomit, refuse to eat, become increasingly lethargic and eventually end up in coma. A metabolic crisis is a life-threatening complication. In argininemia, ammonia does not build up as much as it does in other urea cycle disorders and an episode of metabolic crisis is rare. When children with argininemia have a metabolic crisis because of elevated ammonia levels, it is usually not as severe and not life-threatening like it is in the other urea cycle disorders, but severe episodes can happen.

Argininemia is caused by a change in a gene called ARG1. The National Urea Cycle Disorders Foundation has more information on argininemia. Some infants who were diagnosed and treatment from birth have remained symptom-free through a special diet and medication. This will also stop symptoms from getting worse if they have already begun. Not all infants and children respond to treatment the same.

Argininemia is caused by gene changes in the ARG1 gene. People have about 20,000-25,000 genes in their bodies. Our genes contain our body’s genetic information, called DNA; genes are segments of DNA found on chromosomes. Genes are inherited from our parents and passed on to our children. Genes are like our body’s instruction manual – they control the growth, development and normal function of the body. Genes produce specific proteins that the body needs to grow and work properly. When there is an unexpected change in a gene, the protein that the gene produces may be absent or not work properly or be overproduced.

To find a medical professional nearby who can discuss information about gene changes in the ARG1 gene and argininemia, a listing of medical geneticists can be found at the American College of Medical Geneticists website and genetic counselors can be found on the National Society of Genetic Counselors website.

Argininemia is caused by a change (variant) in the ARG1 gene. Not all changes in a gene necessarily cause disease. If a change is known to cause argininemia, it is known as a pathogenic or disease-causing variant. However, sometimes gene changes are found and scientists are unsure what it means, either because it has not been found before or has only been found in a few people. This is known as a variant of unknown significance. If you have a variant of unknown significance in the ARG1 gene, talk to your doctor about further testing that may help find out whether the gene change is pathogenic or not. A genetic counselor may also be able to help you review your test results. To find a genetic counselor near you who can discuss testing and results, visit the National Society of Genetic Counselors Find a Genetic Counselor website.

If your baby receives a positive result for argininemia from newborn screening, it does not mean that your child definitely has the disorder. Newborn screening can cause "false positives." Further testing is needed to know for sure whether a child has argininemia. Doctors can test a blood sample to detect reduced activity of the arginase enzyme and confirm a diagnosis. This test is called an enzyme assay. Doctors can also confirm a diagnosis through molecular genetic testing. These tests study the ARG1 gene for changes (mutations) that can cause the disorder.

Information about newborn screening can be found at Save Babies Through Screening Foundation or Baby’s First Test.

Rare diseases that affect multiple organ systems like argininemia can benefit from a multidisciplinary approach. This approach involves healthcare professionals with specialized skills and expertise. They work together to make treatment recommendations and to provide quality care of individuals and families. According to the medical literature, infants who were diagnosed and treated at birth have gone symptom-free for their lives with one person more than 35 years old.

If symptoms do develop, then, depending upon the specific symptoms in an individual, a multidisciplinary team may include a specialist for neurological disorders in children (pediatric neurologist) who will monitor the function and health of the brain and central nervous system; a neurologist; a specialist who will monitor the health and function of the liver (hepatologist); a metabolic dietitian who will coordinate the nutritional management of people with metabolic diseases; a nutritionist who can help to develop a special diet; a genetic counselor who can help people understand the disease and the implications for the person and other family members; and a metabolic disease specialist.

Children who have argininemia may benefit from psychological support. This means that they should receive help for any psychological or social problems they may have. Some children may feel different because they must be on a restrictive diet. Others may have learning disabilities or other problems that affect their performance in school. This can cause them to feel different from their friends and can lead to feelings of isolation, anxiousness, depression and frustration.

These are normal feelings for individuals and families dealing with a chronic illness. Talk to your doctor and medical team about how to deal with such issues. Parents and therapists can help children deal with these issues. It is also beneficial to talk to other people and families that are dealing with the same challenges. The National Urea Cycle Disorders Foundation puts people and families who have the same diagnosis in touch with one another. They offer a Mentor Program for newly-diagnosed families as well.

When infants and children have a chronic disorder like argininemia, it can demand a lot of time and focus from parents. As with similar disorders, it is easy for healthy siblings to feel as if they have been pushed aside. Although studies have shown that siblings of children with chronic illness tend to develop strong levels of compassion and empathy, these studies have also shown that siblings can develop feelings of jealousy, anger, and high levels of anxiety. Parents can work with siblings by having clearly defined roles and responsibilities within the family structure. Siblings can help with the care of their sick sibling. Parents are encouraged to make time for activities, especially for healthy siblings, and to talk with and encourage healthy siblings to address their concerns and feelings. Some children may benefit from support outside of the immediate family including therapists or doctors. The Sibling Support Project is a nonprofit organization that serves the concerns and needs of siblings of people with special health, developmental, and mental health needs.

Some infants and children who were promptly diagnosed and treated before symptoms begin, have remained symptom-free. According to the medical literature, this has been true for people who are now more than 35 years old. If symptoms were already present when treatment was started, good results can still be achieved. This is true if treatment is started before significant problems developed. The progression of neurological disease can be stopped and some skills can be reacquired. However, not all infants and children will respond to treatment and treatment cannot repair damage that has already occurred. Consequently, life expectancy will depend on several factors including when the disorder was first diagnosed, what symptoms have already developed and how an individual person or child responds to treatment.

Most infants are normal during the newborn period. They may be irritable, have problems feeding, and may become very sleepy (lethargic) when first introduced to cow’s milk. If untreated, symptoms usually become apparent around 1 to 4 years of age. Children may be clumsy and may fail to gain weight or grow as would be normally expected. The may vomit repeatedly, experience nausea, and may not want to eat (food aversion). They may have delays in reaching developmental milestones and may lose skills that they had already developed. The liver may be enlarged. A children’s head circumference may be smaller than otherwise would be expected, a condition called microcephaly. Some children may walk on their toes. Seizures are common and intellectual disability, tremors, and a condition called spasticity also develop. Spasticity is when there is increased muscle tone and stiffness of leg muscles and can cause muscle spasms. If the disorder remains untreated, the neurological symptoms will worsen and severe intellectual disability, an inability to walk and other severe symptoms can develop.

Sometimes infants or children with argininemia can have a metabolic crisis. This is uncommon, although in other urea cycle disorders it is much more frequent. During a metabolic crisis, an infant may vomit, refuse to eat, become increasingly lethargic, and eventually end up in a coma. A severe metabolic crisis is a life-threatening complication. In argininemia, ammonia does build up as much as it does in other urea cycle disorders and an episode of metabolic crisis is rare. When children with argininemia have an episode, it is usually not as severe and can be treated with intravenous fluids.

Some people have developed damage to the liver and excessive wound healing called hepatic fibrosis. This means a lot of fibrous tissue builds up in the liver. Some people may have scarring in the liver, which is called cirrhosis. These liver problems can be severe enough to require a liver transplant.

If an infant has a positive newborn screening test for argininemia, then further testing will be done to confirm that the child has the disorder. If the diagnosis is confirmed, families should seek a medical consultation with a physician such as a metabolic genetic specialist with experience in treating the disorder. Treatment with special diet that is low in protein and restricts the amino acid arginine should be started immediately. When argininemia has been diagnosed and treated at birth, doctors believe that people can avoid developing symptoms of the disorder. Other initial steps will depend on how the disorder is affecting a person and whether the disorder was diagnosed after symptoms have already begun. If a diagnosis is made after symptoms have begun, then tests will be done to see how far along the disorder and will include neurological tests.

Families should see a genetic counselor to help understand the genetic aspects of this disorder. Families may consider contacting a support group. The National Urea Cycle Disorders Foundation provides information, support, guidance, referrals and networking among other programs for individuals and families affected by urea cycle disorders like argininemia.

Individuals with argininemia should avoid a drug called valproic acid. This is an anti-seizure medication, also called an anti-convulsant. This drug may elevate ammonia levels in people with urea cycle disorders. Unlike other people with urea cycle disorders, those with argininemia should not take receive supplemental doses of the amino acid arginine. While arginine is helpful for other urea cycle defects, this amino acid is already elevated in people with argininemia.

People with argininemia must severely restrict the amount of protein in their diets. Their diet may be called an arginine-restricted diet. Arginine is an amino acid and it builds up in large amounts in people with argininemia. Amino acids a building blocks of protein. Although an arginine-restricted diet is very restrictive, everyone needs some amount of protein. The body gets a lot of its amino acids through its diet. If the body cannot get enough amino acids through its diet, the body will begin to break down its own protein and this will lead to an increase in ammonia in the blood and tissues, and ammonia in high enough amounts is toxic to the brain.

So, when treating a urea cycle disorder like argininemia, doctors and metabolic dietitians must balance the need for some protein against a person’s ability to break down protein. The amount of protein a person with argininemia can tolerate can be different in one person when compared to another person. Many times, the amount of protein a person can tolerate will increase during infancy and childhood as they grow older.

There is newborn screening for argininemia. During routine newborn screening, a tiny sample of blood is taken from the heel of a newborn. This test, called a heel prick, involves getting a few drops of blood from a pinprick in the newborn’s heel. The blood is run through a machine that can detect elevated levels of arginase. Sometimes, newborn screening missing a child with a disorder normally detectable through screening. Other times, there may be a ‘false positive.’ Further testing of a blood sample, called an enzyme assay, can detect reduced activity of the arginase enzyme and confirm a diagnosis.

Information about newborn screening programs can be found at Save Babies Through Screening Foundation or Baby’s First Test.

As of June 2019, there were clinical trials specific to argininemia listed on clinicaltrials.gov, a government website that provides regularly updated information about federally and privately supported clinical trials.

For the most up-to-date list, contact clinical trials.gov and search for argininemia or urea cycle disorders.

Infants with argininemia may be detected through newborn screening (NBS). NBS can detect elevated levels of arginine in the dried blood spots. Further testing of a blood sample, called an enzyme assay, can detect reduced activity of the arginase enzyme and confirm a diagnosis. Doctors may also test the urine for orotic acid (a compound that naturally occurs in the body), but is increased in urine samples from people with argininemia.

Doctors may also conduct molecular genetic testing on infants with argininemia. These tests involve studying the ARG1 gene for changes (mutations) that cause the disorder. This can include sequence analysis, where a part or sequence of DNA within a gene is examined, or deletion/duplication analysis, where missing or extra regions of DNA are looked for within a specific gene. Molecular genetic testing must be done at specialized laboratories.

Argininemia is treated with a special diet. This diet is a low-protein, arginine-restricted diet. Arginine is an amino acid, a building block of protein. People with argininemia cannot properly break down (metabolize) nitrogen, which the body gets from protein in the diet. Because they cannot properly break down protein, ammonia, arginine and other metabolites (byproducts of metabolism) build up in the body. Individuals must remain on this diet for their lives and this can be challenging because the diet is very restrictive. Because protein intake is significantly reduced, people with argininemia will need to receive a supplement that provides essential amino acids that they normally would get through eating protein. Parents and individuals should work closely with a metabolic dietitian in planning their diets. To find a metabolic dietitian specializing in diets for people with metabolic conditions, visit the GMDI Find a Metabolic Dietitian webpage.

Doctors may also use medications that are called nitrogen scavengers. These drugs help to remove nitrogen from the body. These drugs create a different way to break down and remove nitrogen from the body; this is called alternate pathway therapy. These drugs include Ammunol®, Buphenyl®, and Ravicti®.

Unlike other urea cycle disorders, most infants and children with argininemia do not have severe episodes of excess ammonia in the body. A mild episode can be treated with intravenous fluids. Sometimes, nitrogen scavenging drugs may also be used.

If ammonia is highly elevated in the body, this is called a hyperammonemic crisis. It may also be called a metabolic crisis. This is a medical emergency and will require hospitalization. Sometimes, doctors must use dialysis to remove the ammonia from the blood. This is the quickest way of removing excess ammonia from the body. Several different methods are available and hemodialysis is considered the fastest.

Seizures can usually be effectively treated with anti-seizure (anti-convulsant) medications.

Some people with argininemia developed damage and scarring of the liver (cirrhosis). People with argininemia have been treated with a liver transplant. A liver transplant has corrected the underlying genetic defect in argininemia. It restores the missing enzyme, arginase. However, a liver transplant cannot repair damage to the brain that has already occurred. There are also significant risks. Risks involved with a transplant procedure include the body rejecting the transplant (graft versus host disease), the transplant failing, serious infection, and other potential complications. Parents should make decisions about this treatment in close consultation with doctors and other medical personnel who are experienced with argininemia.

A patient registry is a database set up by researchers that contains information about patients with a particular disorder or group of disorders. This information helps researchers learn about a disorder, plan or study treatments, how a disorder progresses or affects people and other information. Patient registries require that patients either directly or through their doctor submit personal information. There is a patient registry for urea cycle disorders called The Urea Cycle Disorder International Patient Registry. The European Registry and Network for Intoxication type Metabolic Disorders has a European registry for urea cycle disorders.

Talk to a genetic counselor about the pros or cons of participating in a patient registry. Genetic counselors can be found on the National Society of Genetic Counselors website.

Carriers of an altered ARG1 gene that causes argininemia do not develop symptoms of the disorder. They are at risk of passing the disorder on to their children if their partner is also a carrier. A genetic counselor in your area can help you understand more about your risk and the testing options for carriers.

The cost of special medical food for argininemia can be different for one person or family when compared to another. There are many factors to consider. The supplier, the specific formula and medical foods, whether a person has insurance, whether the insurance plan will cover special medical foods, how much protein a person can handle in their diet, and other factors. For this reason, it is difficult to give an approximation about how much the use of medical food product would cost any given person. The cost is much more than it would be feed someone without argininemia, and can be very expensive for an average family.

In the 2013 session of Congress, a bill has been introduced call the Medical Foods Equity Act. It has not been passed. This bill would require all federal programs to cover the cost of medical foods (formula and foods modified to be low in protein) for children and adults with argininemia and similar disorders that require a special diet and supplemental medical foods.

Contact the National Urea Cycle Disorders Foundation (NUCDF) to learn about how much an arginine-restricted diet and supplemental medical foods may cost your family. The NUCDF may also have advice for dealing with insurance companies, information on state laws and policies on medical food and formula coverage, and links to the best places to find these products.

People with argininemia remain on a special diet for life. When people stop following the diet, they will begin to experience problems, even if those problems aren’t obvious. Some of the neurological damage associated with argininemia cannot be repaired once it has happened. The diet is a low-protein, arginine-restricted diet. It is a very restrictive diet overall and doctors know that some patients have trouble staying on the diet. Doctors strongly advocate that people with argininemia follow their special diet for life, and that people who have given up on the diet start following again as soon as possible. Parents and individuals should work closely with a metabolic dietitian in planning their diets. To find a metabolic dietitian specializing in diets for people with metabolic conditions, visit the GMDI Find a Metabolic Dietitian webpage.

We each get two copies of most of our genes from our parents. One copy comes from our mother and the other copy comes from our father. In argininemia, both parents must pass along a nonworking copy of the ARG1 gene. Because of this, argininemia is inherited in what is called an autosomal recessive pattern. People who have one working and one nonworking copy of the ARG1 gene are called carriers. When both parents are carriers, for each individual pregnancy, there is a 25% chance that both parents will pass along a nonworking copy of the gene and the child will have the disorder. There is a 50% chance that one parent will pass on the gene change and the other will not, meaning the child will be a carrier for the disorder. Finally, there is a 25% chance that both parents will pass along a working copy of the gene and the child will not have the disorder and will not be a carrier.

If you are interested in finding out if you are a carrier for argininemia, talk to your doctor about testing or contact a [link url=https://www.nsgc.org/page/find-a-genetic-counselor” target=”_blank”>genetic counselor in your area.

Argininemia is inherited in an autosomal recessive manner. This is one way a disorder or trait can be passed down through a family. Everyone has two copies of the ARG1 gene; one received from their father and one from their mother. Autosomal recessive inheritance means that a person receives a nonworking copy of the ARG1 gene from both parents. The parents have one working copy of the gene and one nonworking copy; they are carriers for argininemia. Carriers do not develop symptoms of the disorder. If two people are carriers, there is a 25% chance with each pregnancy that the child will have the disorder and a 50% chance the child will also be a carrier for the disorder. If you have a family member with argininemia and you would like to know if you are a carrier, talk to your doctor or meet with a genetic counselor to discuss testing options.

Argininemia can be classified as a urea cycle disorder or an amino acid disorder. People with this disorder have problems with an enzyme called arginase I. This enzyme is missing, deficient, or damaged. The arginase I enzyme has a job. It is part of the urea cycle. This cycle is series of biochemical reactions that occur in the body to help to break down (metabolize) and then remove excess nitrogen from the body. Nitrogen is obtained from the diet and is a normal waste product of the metabolism of protein. Nitrogen is broken down into a compound called urea that is excreted from the body in the urine. People with argininemia cannot properly break down the arginine, which is a step in the urea cycle. Because they cannot break down arginine and cannot completely convert nitrogen into urea, arginine and nitrogen (in the form of ammonia) build up in the body. Arginine, which is found in elevated levels in people with argininemia, is an amino acid. Amino acids are chemical ‘building blocks’ the body uses to produce certain proteins that are required for proper growth and development. Therefore, argininemia is both a urea cycle disorder and an amino acid disorder.

Argininemia is caused by a change in a gene called ARG1. This gene produces an enzyme known as arginase I. Because of the gene change, people with argininemia do not produce enough, or produce a damage form of this enzyme. Arginase I has a job. It is involved in the last step of the urea cycle. This cycle is series of biochemical reactions that occur in the body to help to break down (metabolize) and then remove excess nitrogen from the body. Nitrogen is obtained from the diet and is a normal waste product of the metabolism of protein. Nitrogen is broken down into a compound called urea that is excreted from the body in the urine. People with argininemia cannot properly break down the amino acid arginine, one step of the urea cycle. An amino acid is a building block of protein. Because they cannot break down arginine and cannot completely convert nitrogen into urea, arginine and nitrogen (in the form of ammonia) build up in the body.

Ammonia is a neurotoxin, it damages cells of the central nervous system (which is made up of the brain and spinal cord). Ammonia does not build up in argininemia as much as it does in other urea cycle disorders. People with argininemia rarely have a severe metabolic crisis that is common in other urea cycle disorders. During a metabolic crisis, an infant may vomit, refuse to eat, become increasingly lethargic, and eventually end up in coma. A metabolic crisis is considered a life-threatening complication.

Doctors do not understand exactly why symptoms develop in argininemia. Unlike other urea cycle disorders, they do not believe that ammonia plays a big role in the develop of symptoms. Ammonia is not elevated in the same amount as it is in other urea cycle disorders. Doctors know that, if untreated, the persistently elevated levels of arginine and its metabolites (substances formed during metabolism) in the body and the blood most likely play significant roles. Doctors are still trying to determine how a deficiency of the arginase I enzyme causes the symptoms of argininemia

Argininemia can be diagnosed after a positive result from newborn screening. During routine newborn screening, a tiny sample of blood is taken from the heel of a newborn. This test called a heel prick or Guthrie test involves getting a few drops of blood from a pinprick in the newborn’s heel. The blood is run through a machine that can detect high levels of arginine, an amino acid that abnormally builds up in people with argininemia. Sometimes, newborn screening may miss an infant with argininemia, and sometimes there may be a false positive.

Additional tests will be performed to confirm the diagnosis. These tests involve looking at the blood and urine for substances that are abnormally elevated in argininemia including arginine and orotic acid. The blood may be tested to see if the activity of the arginase enzyme is reduced. This is called an enzyme assay.

Doctors may also conduct molecular genetic testing on infants with argininemia. These tests involve studying the ARG1 gene for changes (mutations) that cause the disorder. This can include sequence analysis, where a part or sequence of DNA within a gene is examined, or deletion/duplication analysis, where missing or extra regions of DNA are looked for within a specific gene. Molecular genetic testing must be done at specialized laboratories.

If you believe your child may have argininemia, talk to your pediatrician or a genetic counselor about your concerns. They can help decide if testing is right for you, and can order this testing if necessary.

To learn about ongoing clinical research into argininemia ask a physician who specializes in the disorder. Genetic counselors and medical geneticists are also excellence sources of information about ongoing clinical trials and can offer advice about the pros and cons about participating in such a trial.

Ongoing studies for argininemia can also be found on clinicaltrials.gov, a service of the U.S. National Institutes of Health. In Europe, the EU Clinical Trial Register performs a similar service.

Support groups also have information about ongoing clinical trials as well as information and advice about participating in clinical trials. Support groups for argininemia include the National Urea Cycle Disorders Foundation.

There are medical clinics around the U.S. and genetic clinics that can help people with metabolic disorders like argininemia. The National Urea Cycle Disorders Foundation may be able to help you find a clinic or physician treating argininemia near you. A medical geneticist and metabolic nutrtionist will be helpful for you. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. If you are looking for a metabolic clinic for treatment in the United States, you can search for the clinic or clinics in your state.The Genetics and Rare Diseases Information Center has information on how to find a disease specialist.

Some people with argininemia find it challenging when it’s time to move (transition) from pediatric to adult health care services. One big change is leaving a doctor with whom you have a long-standing relationship, a doctor who is familiar with both your condition and you. It can feel like ‘starting over’ as you’ll begin to work with new doctors and a new medical team. Another challenge in moving to adult care is that young adults must take greater responsibility for their health. They must manage their disorder and manage their medications. They must bear greater responsibility for decisions concerning their health. Adolescents should be encouraged to make decisions about their care as early as possible to make this transition easier. Some hospitals have programs to help children with chronic disease transition to adult care services.

Support groups may also provide information or support on how to move from pediatric care to adult care services and what to expect. The National Urea Cycle Disorders Foundation provides information and support for families dealing with argininemia.

Some children with argininemia may have intellectual disability or experience delays in reaching developmental milestones. This can make school more challenging. These children may need special accommodations in school. They are eligible for an individual education plan (IEP) or a 504 plan.

An IEP is a document that helps to guide the education of a child with a disability or special needs and ensures that they have access to the same educational opportunities as all children. The plan is individualized for each student.

A 504 plan ensures that students with disabilities can fully participate in school and have access to the same educational opportunities as all children. This plan is important for making sure a student with galactosemia can maintain their diet while fully participating in school with the same access to educational opportunities as all children.

Even children who received an early diagnosis and prompt treatment and do not have symptoms are eligible for a 504 plan. A 504 plan organizes any unique requests needed by a child to fully participate in school. This plan is important for making sure a student with argininemia can maintain their diet in school while fully participating in school with the same access to educational opportunities as all children.

Parents should talk to their child’s school system and learn what they need to do for their children. Parents are encouraged to provide a school with a packet of information on argininemia and to work with school officials including teachers, nurses, psychologists, the principal, and other professionals. The National Urea Cycle Disorders Foundation has a guide for educating school officials called, An Educator’s Guide to UCD.

The U.S. Department of Education has information on individual education plans and on 504 plans. Global Genes, a rare disease advocacy organization, has a RARE Toolkit that advises parents on advocating for their children at their school.

Argininemia is a rare disorder. Rare disorders often go unrecognized or misdiagnosed and the incidence and prevalence of individual rare disorders is often unclear or unknown. Prevalence is the measurement of all individuals affected by the disease at a particular time. Incidence is the amount of new people with a disorder or newly-diagnosed. The incidence of argininemia has been estimated to anywhere from 1 in 300,00 to 1 in 2,000,000 people in the general population. The incidence may vary based on different populations examined. Argininemia is classified as a urea cycle disorders. The incidence of these disorders, collectively, is about 1 in 30,000 people. Argininemia is one of the least common urea cycle disorders.

If untreated, argininemia can cause neurological symptoms including intellectual disability. Most infants do not show any symptoms until 2-4 years of age. Intellectual development may slow and these children may have delays in reaching developmental milestones. If these children remain untreated, severe intellectual disability can result. If treatment is started before symptoms begin, some people have remained symptom-free well into adulthood. If treatment is started early after symptoms begin, it can stop neurological decline and some children may regain some skills. However, treatment cannot repair damage that has already occurred and not all children will respond to treatment.

Talk to your doctor and medical team about your child’s development. A pediatric neurologist should be part of the medical team. The Arc is an organization dedicated to providing support and information for people with intellectual and developmental disabilities.

There are several things that can make a urea cycle disorder worse. These include eating a lot protein in the diet, undergoing a surgical procedure, having another illness like a viral infection, or the use of certain drugs like valproic acid, which is used to treat seizures. These create stress on the urea cycle, the series of biochemical steps through which the body breaks down (metabolizes) and removes nitrogen from the body. Nitrogen is obtained from protein in the diet. The factors describe can lead to a buildup of ammonia and arginine and its metabolites (normal byproducts of metabolism) in the blood and the body. A woman’s menstrual cycle is also believed to contribute to elevated levels of ammonia in argininemia. Most times, people with argininemia do not have significantly elevated levels of ammonia in the body and can be treated with intravenous fluids. However, significantly increased ammonia levels can occur and is a life-threatening complication the requires hospitalization.

One study of 6 people with argininemia found an increased risk of a coagulation (blood clotting) disorder even if there were not other signs of a coagulation disorder. Because this study is so small, we are not able to say what the risk might be for all people with argininemia to have a coagulation disorder. However, you might want to speak with your doctor about monitoring you or an affected family member for a coagulation disorder.

People with argininemia should be able to travel safely and enjoyably. People or families need to be prepared when traveling, particularly when traveling by air or internationally. If you are traveling and you or your child has argininemia, you may want to bring a letter from your physician explaining the medical necessity of any food or formula you are bringing with you. You may also carry information about their condition when they travel in case there is a medical emergency. People with argininemia should have an emergency card that explains their disorder. If you are traveling abroad, you may want to contact your medical team to see where appropriate food and formula can be obtained and whether your destination has adequate medical facilities.

How families travel with a child with argininemia can also depend on the amount of neurological problems a child has. Support groups and other parents or families with argininemia can offer advice and information and how to make traveling easier and safer. Support groups for argininemia include, The National Urea Cycles Disorders Foundation.

Some parents may choose to have their child tested for argininemia before they are born. This is known as prenatal diagnosis. If the gene change(s) that causes argininemia are known in a family, then molecular genetic testing (which can detect these changes) can be used for prenatal diagnosis. A sample of tissue can be taken from the placenta to test for changes in the ARG1 gene. This test is called chorionic villus sampling. Another test is called amniocentesis, which involves taking a sample of the amniotic fluid that surrounds and protects a developing fetus. Cells known as amniocytes are taken from the fluid and studied for changes in the ARG1 gene. There are risks to the unborn baby of doing these tests before birth.

If molecular genetic testing is not possible, doctors can make a prenatal diagnosis through biochemical testing. This is testing to measure the activity of the enzyme arginase, which is significantly reduced in argininemia. Doctors test fetal red blood cells taken from a sample of umbilical cord blood after 18 weeks gestation. Severe reduction of arginase activity indicates a diagnosis of argininemia. In other disorders, samples of tissue or cells from the amniotic fluid or placenta are used. They cannot be used to diagnose argininemia because these tissues do not have any arginase activity.

Prenatal diagnosis of conditions that are treatable like argininemia are not common, although different medical professionals may have different opinions about whether it is appropriate. Talk to your doctor or a genetic counselor in your area to discuss the risks and benefits of prenatal diagnosis.

Argininemia is one name that doctors and medical professionals may use to describe this disorder. Other names include,

Support groups are organizations that provide support, information, advice, referrals to physicians and medical centers, and up-to-date information on research and treatments. The National Urea Cycle Disorders Foundation is a nonprofit organization dedicated to the identification, treatment and cure of urea cycle disorders.

There are also organizations that provide support and information for metabolic disorders like argininemia as a group. These organizations are called umbrella organizations. They represent many different metabolic disorders including the urea cycle disorders and include Children Living with Inherited Metabolic Diseases and the European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD).

Most children with argininemia do not show symptoms until 2-4 years of age. Some will show symptoms as newborns. If treatment is started from birth, they may remain symptom-free. If symptoms develop they include neurological problems that can include intellectual decline. Treatment can stop neurological problems from getting worse and some children may regain lost skills, but treatment cannot repair neurological damage that has already happened and not all children respond to treatment.

The first few years of a child’s life are critically important to a child’s development. States have federally-funded early intervention programs that support families that have concerns or issues with their children’s development up to the age of three. Some states will continue to offer early intervention programs beyond the age of three. Other states will transition a child into school-based programs that can be provided at home. In some states, a child may be eligible for early intervention services at no charge. Other states may charge a fee, depending on the agencies involved.

Talk to your doctor and medical team about early intervention programs in your state and whether these resources will appropriate and beneficial for your child. The Centers for Disease Control and Prevention (CDC) provide information about early intervention programs and assistance.

One disorder that argininemia may be mistaken for is cerebral palsy. Both disorders cause spasticity. This is a medical term that describes when muscles, usually of the legs, become taunt and stiffen. The muscles become difficult to stretch and people may have slow, writhing motions with their movements. There is a large group of genetic disorders that also causes spasticity called hereditary spastic paraplegia.

People with argininemia must continually have their blood monitored to measure the amount of arginine and ammonia in the blood. The function of the liver must also be tested periodically to ensure that liver function is not affected. Different doctors and different hospital may do this testing differently and how often this testing is done can vary as well. The amount of time between testing will depend on several factors. The amount of protein a person with argininemia can tolerate will be different based on their ages, how severe their disorder is, how quickly they’re growing, and the whether they have another illness like the flu. If people with argininemia become sick this may put stress on the urea cycle. If a child or person with argininemia gets sick, like a viral illness, they should be seen immediately by a doctor and have their ammonia and arginine levels checked.

Parents of children with argininemia and people with the disorder should work with their doctors and entire medical team so they can work out a system for monitoring blood arginine and ammonia levels. Parents should consider working with their children so it will easier one day for the children to take over their own monitoring.