Argininosuccinase deficiency, also known as citrullinemia, describes a hereditary disease where citrulline and ammonia build up in the blood. Ammonia is a very toxic substance and when it accumulates in the bloodstream, it can travel to the brain, causing severe neurological problems. Some infants can have symptoms within just a few days of birth.
The Urea Cycle
Ammonia is very toxic to the nerves, even in very small amounts. Thus, when the cells break down certain amino acids and ammonia is one of the products formed, the ammonia is sent to the liver and changed to urea in a process called the urea cycle, according to the “Principles of Medical Biochemistry” by Gerhard Meisenberg, Ph.D., a biochemistry professor at Ross University School of Medicine. The urea cycle involves several steps. The second step changes the amino acid citrulline to argininosuccinate. To accomplish this, however, the cells must use an enzyme called argininosuccinic acid synthetase.
Argininosuccinase Deficiency and Citrulline
Enzymes are simply proteins the cells must use to make a reaction go faster. A person with argininosuccinase deficiency does not have enough of the argininosuccinic acid synthetase enzyme and, as a result, a high amount of citrulline accumulates in the bloodstream; the medical term for this is citrullinemia. According to the National Institutes of Health, argininosuccinase deficiency is caused by mutations in a gene named ASS1, because this is the gene which tells the cells how to make the argininosuccinic acid synthetase enzyme. This enzyme is also called argininosuccinate synthetase; the deficiency is also referred to as classic citrullinemia and Type 1 citrullinemia.
Symptoms
Infants may seem normal when born, but citrulline and ammonia will build up in a few days and cause vomiting, problems with feeding, seizures, a lack of energy and breathing problems. Infants with a milder form may not have any symptoms until childhood or perhaps not even until adulthood; then they may feel tired, have partial vision loss, a lack of coordination and balance and severe headaches. If the form is mild enough, they may never have any symptoms. Whether or not they have symptoms and the degree depends on the accumulation of citrulline and ammonia in the brain, explains Allan Ropper, M.D., a neurology professor at Harvard Medical School in “Adams & Victor’s Principles of Neurology.”
Treatment
A physician will usually diagnose argininosuccinase deficiency when the patient is an infant; treatment can then begin. Limiting the amount of protein helps, because proteins are broken down to amino acids, according to the University of Maryland Medical Center. Less protein means less amino acids and therefore less ammonia. Infants can be given a low-protein formula; the physician can determine the proper balance of protein. Too much will bring excessive ammonia in the bloodstream. Someone with this disorder must realize that stress, like fever and infections, can result in cells breaking down their proteins, creating amino acids and ammonia.
References
- “Adams & Victor’s Principles of Neurology”; Allan Ropper, M.D., Martin Samuels, M.D.; 2009
- “Harper’s Illustrated Biochemistry”; Robert Murray, M.D., Ph.D., David Bender, Ph.D. et al.; 2009
- National Institutes of Health: Citrullinemia
- “Principles of Medical Biochemistry”; Gerhard Meisenberg, Ph.D., William Simmons, Ph.D.; 1998
- “University of Maryland Medical Center"; Hereditary Urea Cycle Abnormality - Overview; Chad Haldeman-Englert, M.D.; January 2010
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