Background Argininemia is a rare Urea Cycle defect caused by deficiency of Arginase in liver and erythrocytes. Arginase is the final enzyme in the Urea Cycle that catalyzes the breakdown of arginine to ornithine and urea, which is the major metabolite carrying waste nitrogen destined for urinary excretion. Patients with Arginase deficiency have elevated levels arginine in blood. The deficient Arginase gene is located on chromosome 6. Clinical Patients with Argininemia may present from two months to four years of age. Symptoms are progressive spastic paraplegia, failure to thrive, delayed milestones, hyperactivity and irritability, with episodic vomiting, hyperammonemia and seizures. Mental retardation is a result of cerebral atrophy which leads to microcephaly. Hepatomegaly may be present. Testing Argininemia may be detected by newborn screening using tandem mass spectrometry of a dried blood spot. Affected patients have elevations in arginine ranging from 5- to 10-fold, while other amino acids are usually in the normal range. Arginase enzyme activity can also be eluted and measured from the dried blood spot. Hyperammonemia is moderately severe. The patient’s urine contains elevated levels of orotic acid, along with increased levels of the diamino acids: arginine, lysine, cystine and ornithine. The deficient Arginase activity is tissue specific for the liver and erythrocyte. Heterozygous carrier individuals have partially reduced enzyme activity, but are clinically unaffected. Several mutations have been reported in the gene. Identification of the mutations allows prenatal diagnosis and genetic testing for other family members. Treatment Argininemia is a rare disorder and few patients have been treated from an early age, prior to onset of disabling symptoms. Dietary restriction of protein is the basic treatment, with supporting therapy to prevent and control the hyperammonemia. Because the diagnosis and therapy of argininemia is complex, the pediatrician is advised to manage the patient in close collaboration with a consulting pediatric metabolic disease specialist. It is recommended that parents travel with a letter of treatment guidelines from the patient’s physician. Inheritance This disorder most often follows an autosomal recessive inheritance pattern. With recessive disorders affected patients usually have two copies of a disease gene (or mutation) in order to show symptoms. People with only one copy of the disease gene (called carriers) generally do not show signs or symptoms of the condition but can pass the disease gene to their children. When both parents are carriers of the disease gene for a particular disorder, there is a 25% chance with each pregnancy that they will have a child affected with the disorder. As with all genetic diseases, genetic counseling may be appropriate to help families understand recurrence risks and ensure that they receive proper evaluation and care.
References Brusilow, S. and Horwich, A. Urea Cycle Enzymes. In, The Metabolic and Molecular Basis of Inherited Disease. 8th Edition, 2001. Scriver, Beaudet, et al. McGraw-Hill. Chapter 85, pg. 1909-1963. Bernar, J., Hanson, R.A., Kern, R., et al. Arginase deficiency in a 12 year old boy with mild impairment of intellectual function. J Pediatrics 108:432, 1986. Qureshi, I.A., Letarte, J., Ouellet, R., et al. Treatment of hyperargininemia with sodium benzoate and arginine restriction diet. J Pediatrics 104:473, 1984.
Web Sites SaveBabies.org
Site established and maintained by parents of newborns affected with a rare genetic defect, with information for parents and professionals and links to other informative sites. National Newborn Screening and Genetics Resource Center
Provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.
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The analyses conducted by PerkinElmer Genetics produce results that can be used by qualified physicians in the diagnosis of disorders described herein. Evidence of these conditions will be detected in the vast majority of affected individuals; however, due to genetic variability, age of the patient at the time of specimen collection, quality of the specimen, health status of the patient, and other variables, such conditions may not be detected in all affected patients. PerkinElmer Genetics makes no warranty whatsoever, express or implied, including any warranty as to accuracy, completeness or timeliness, concerning the information contained herein, and you should not assume that such information is complete or the most up-to-date information available. PerkinElmer Genetics shall not be liable for any loss, claim or damages caused in whole or in part by our provision of, or your use of, any of the information contained herein. As a general statement, this information was drawn from published literature and is not drawn from our patient population or screening experience. The information contained herein is not intended to be a substitute for professional medical advice and should not be used for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions.
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