Argininosuccinic acid disease is a metabolic disorder that is already congenital. It is caused by a defect in the enzyme argininosuccinate lyase.
What is argininosuccinic acid disease?
Argininosuccinic acid disease (argininosuccinaturia) is a congenital urea cycle defect. Urea, which is one of the organic compounds, is formed in the liver. Urea is of considerable importance for numerous biological processes. These include, for example, protein metabolism. In addition, the excretion of nitrogen, the uptake of which takes place with dietary protein, occurs as urea through the urine. The formation of urea is called the urea cycle. Several enzymes participate in it. One of these enzymes is argininosuccinate lyase. If there is a deficiency of it, this results in argininosuccinic acid disease. In this case, the concentration of argininosuccinic acid increases in all body fluids. In addition, the protein building block citrulline, ammonia and orotic acid are present in the blood. How pronounced the symptoms of arginosuccinic acid disease are depends on how much the ammonia increases within the blood. Ammonia is a chemical compound of hydrogen and nitrogen. In higher concentrations, it produces a toxic effect.
Causes
Mutations that occur within the ASL gene are responsible for arginosuccinic acid disease. The ASL gene is located on chromosome 7 and provides for the coding of argininosuccinate lyase. Normally, it catalyzes the division of argininosuccinate into arginine and fumarate. However, if a gene defect is present, the urea cycle can no longer run smoothly. This in turn results in the accumulation of argininosuccinate, citrulline and ammonium in the blood. Argininosuccinic acid disease is one of the rare hereditary diseases. Thus, it is inherited in an autosomal recessive manner. In the United States and Europe, approximately one in 215,000 newborn infants develops the disease.
Symptoms, complaints, and signs
The first symptoms due to argininosuccinic acid disease usually appear immediately after the birth of the affected child, but may also occur later during childhood. In medicine, a distinction is made between three courses of the hereditary disease. These are the early neonatal form, the acute form, and the chronic form, which sets in late. In the early form, the ammonia within the blood already increases in the first days of life. In this case, the affected infants suffer from weak drinking, trembling, muscle weakness, slowed reactions, frequent vomiting, lethargy and seizures. Doctors then also speak of a hyperammonemic episode. If the neonatal form is not treated in time, the sick infant is at risk of coma, which is often fatal. The infantile acute form can begin as early as infancy. Here, too, seizures and vomiting occur. Other symptoms include dry and scaly skin, involuntary movements and loss of consciousness. Enlargement of the liver is also possible. Without effective therapy, there is a risk of mental or physical disability. The late form, which takes a chronic course, is seen in young children. In this case, delayed development is initially the main feature. As it progresses, there is a risk of slowed reactions, tremors and seizures. Some children may also suffer from headaches or infections such as colds and coughs. A typical feature is also the development of brittle and shaggy hair, which is known as trichorrhexis nodosa. A hyperammonemic episode may also be manifested in the late form by the excessive ingestion of proteins or flu-like infections. If the chronic form remains undetected due to a mild course, there is a risk of long-term sequelae. These include. Liver disease such as cirrhosis and high blood pressure or cognitive impairment such as ADHD or learning disabilities, respectively.
Diagnosis and progression
Argininosuccinic acid disease can be detected by its typical features. Thus, argininosuccinic acid increases in the blood. There are also changes in the concentration of protein building blocks such as arginine, ornithine, and citrulline, which can be detected by special laboratory testing.The enzyme argininosuccinate lyase is detected in fibroblasts (skin cells), erythrocytes (red blood cells), and kidney and liver tissue. The concentration of argininosuccinic acid does not affect the extent of hereditary disease. The course of arginosuccinic acid disease depends on which form of the disease the affected child suffers from. The prognosis is considered unfavorable in the neonatal form. However, the prognosis is better in mild forms of the disease, provided that consistent therapy is undertaken. In addition, there must be no metabolic derailments. Furthermore, a special diet is necessary to counteract mental disabilities.
When should one go to the doctor?
In most cases, argininosuccinic acid disease is diagnosed right after the baby is born while still in the hospital. However, in some cases it may not appear until some time after birth, so a visit to a doctor for diagnosis is then necessary. This doctor should be consulted especially if there is vomiting and muscle weakness. Likewise, most patients also suffer from severe tremors. If the symptoms occur, then a doctor should be consulted. Argininosuccinic acid disease may also be present in cases of loss of consciousness or involuntary movements. It is not uncommon for patients to also suffer from symptoms of a cold or flu, but these are permanent and do not disappear. Patients are also susceptible to minor illnesses and infections and suffer from a weakened immune system. Likewise, a medical professional should also be consulted in the case of high blood pressure. Treatment is usually possible, so that the symptoms can be limited in the long term. In most cases, this also does not reduce the life expectancy of the patient.
Complications
The disease has three courses, with the neonatal form posing the most severe problems. The resulting complications are manifested in developmental delays as well as severe abnormalities in the growing child. Among other things, the child suffers from seizures, muscle weakness, vomiting, susceptibility to infections, headaches, enlarged liver, coma, circulatory failure and even death. If parents recognize the signs of illness too late, the infant may succumb to the symptom. Infants often show ADHD symptoms, vomiting, tremors, and flaky hair and skin. To rule out serious complication consequences, the child belongs in medical care. Even in the late variant of the course, which can break out at any age, health consequences threaten. Liver cirrhosis and cognitive impairment may develop. The syndrome can be reliably detected by a special laboratory test. A long-term treatment plan is then created based on the findings. If the symptom is detected early, late complications can be effectively avoided. Important features are a low-protein diet and medical preparations that specifically counteract the ammonia increase.
Treatment and therapy
The therapy of argininosuccinic acid disease depends on the particular form of the disease. If the neonatal form is present, the goal is to stop the ammonia from multiplying. This is also done in the case of other urea defects. Long-term treatment is an important part of the therapy. In the course of this treatment, the affected child receives drugs that counteract ammonia proliferation. These include phenylbutyrate and sodium benzoate, which are administered intravenously. The body also receives glucose and lipids. Also of importance is a special diet. For example, the intake of proteins must be significantly reduced to prevent the ammonia from multiplying. To meet the need for vital protein building blocks, the child receives special medication. High-protein foods that the child must avoid include milk and dairy products, meat, sausage, fish, legumes, eggs, nuts and semolina. On the other hand, fruits, vegetables, potatoes, rice, applesauce, and low-protein bread and pasta are considered reasonable.
Outlook and prognosis
The prognosis of argininosuccinic acid disease depends on the patient’s treatment. Without medical care, the newborn may develop a comatose state within the first few days of life. The risk of death in these cases is very high.If medical treatment is given very late, the infant faces a similar unfavorable prognosis. If the child survives, sequelae and lifelong impairments are possible. There is a better chance of health improvement for newborns who are examined immediately after birth and treated without delay after diagnosis. If there are other diseases, the state of health is classified as critical. The prognosis depends on the severity of the illnesses. Without further impairments, a comprehensive treatment plan is applied. The inborn errors of metabolism show individual symptoms. These are treated individually with targeted medications or coordinated therapies. A cure for argininosuccinic acid disease does not occur, as it is a disease of the metabolic system. However, it can be supported and specifically influenced. Thereby the occurring complaints are alleviated and partly completely treated. With a special diet and by observing various medically necessary factors, it is possible to achieve a significant improvement in the patient’s well-being. He is enabled to live well with the disease as well as largely without additional impairments.
Prevention
Prevention against argininosuccinic acid disease is not possible. Thus, it is a hereditary disease that is already congenital.
Follow-up
Follow-up care for the rare argininosuccinic acid disease is often omitted because affected individuals die at a young age from the metabolic disease due to ASL deficiency. The inherited urea cycle defect can manifest at any age, even in newborns. The most precarious hallmark of argininosuccinic acid disease is hyperammonemic coma. However, symptoms resembling psychosis may occur beforehand. This complicates the diagnosis. In fact, however, an excess of ammonium in the blood is the cause. If argininosuccinic acid disease has been diagnosed in a patient who is already elderly, he or she will require treatment and intensive follow-up care for the rest of his or her life. It is important to realize that mild and undiagnosed courses of argininosuccinic acid disease can also occur. Therefore, the symptomatology of ALS deficiency can vary greatly from individual to individual. However, if left untreated, the chances of those affected to live a symptom-free and long life decrease. An acute excess of ammonium in the organism can occur at any time. Doctors try to achieve relief by maintaining a strictly low-protein diet for the rest of the patient’s life. At the same time, in both short-term and long-term therapy, the amino acid L-arginine, and additionally sodium phenylbutrate or sodium benzoate are administered to bind the excess ammonium. At the end of all medical options, often only a liver transplant remains. Here, follow-up care is even far more important because of the potential for rejection and infection.
What you can do yourself
The most important contribution to self-help is made by an affected person in which he or she eats disease-specific food. In both acute and long-term therapy, one of the most important measures is to reduce protein intake so that less ammonia is formed. Patients must therefore look at their eating habits and learn which foods are particularly rich in protein and what alternatives are available that they can tolerate. Unlike many other diseases that are influenced by diet, vegan alternatives are not always preferable in argininosuccinic acid disease. The body’s ammonia production is boosted by both animal and pure plant protein. In general, meat, sausage, eggs, egg pasta, milk, yogurt, cottage cheese, cheese, legumes, seeds and nuts, especially peanuts should be avoided. Since soy and especially lupins are high in protein, it is not worth switching from cow’s milk products to products based on these two plant species. However, cow’s milk can be replaced by comparatively low-protein rice milk. Those affected should have an ecotrophologist put together a diet plan and, based on this, develop a meal plan for the entire next week. It is also worth investing in a good nutrition table that not only shows the calories but also the protein content of foods.
