The hepatic urea cycle is the major route for waste nitrogen disposal, which is generated chiefly from protein and amino acid metabolism. Low-level synthesis of certain cycle intermediates in extrahepatic tissues makes a small contribution to waste nitrogen disposal as well. A portion of the cycle takes place in mitochondria. Overall, activity of the cycle is regulated by the rate of synthesis of N-acetylglutamate, the enzyme activator that initiates incorporation of ammonia into the cycle.
The reaction normally mediated by arginase is the terminal step in the urea cycle, which liberates urea with regeneration of ornithine. Consequently, as in argininosuccinic aciduria, both waste nitrogen molecules normally eliminated by the urea cycle are incorporated into the arginine substrate molecule in the reaction.
Think that is complicated? Look at THIS.
As an inherited disorder, the age of onset is typically during the neonatal period(or in simpler terms, the early part of infancy). Because of its atypical form of manifestation, the disease may be easily missed in the neonatal period and only recognized in later infancy or early childhood. Some cases likely go undiagnosed, with clinical symptomatology attributed to cerebral palsy. Also, being an inherited disorder, parents have 1 in 4 chances of having an affected child with each conception. Affected infants and children may exhibit mental retardation, seizures, and spasticity (difficulty in walking).Luckily, arginase deficiency hardly results in death. yay!
Diagnosis is made by special blood tests called plasma amino acids. Enzyme level can be measured in the blood however specialized laboratory help is required for this. In some situations DNA mutation analysis is also available. To prevent giving birth to an affected child, prenatal diagnosis is possible based on DNA mutation analysis.
But if YOU have arginase deficiency (touch wood), this is what you should do!
1. Normalize plasma arginine levels
2· Go for genetic counselling
3· Take a low protein diet
4· Take these drugs: Sodium phenyl butyrate/ benzoate to divert nitrogen from urea cycle
3 comments:
Arginase deficiency usually becomes evident by about the age of 3. It most often appears as stiffness, especially in the legs, caused by abnormal tensing of the muscles (spasticity). Other symptoms may include slower than normal growth, developmental delay and eventual loss of developmental milestones, mental retardation, seizures, tremor, and difficulty with balance and coordination (ataxia). Occasionally, high protein meals or stress caused by illness or periods without food (fasting) may cause ammonia to accumulate more quickly in the blood. This rapid increase in ammonia may lead to episodes of irritability, refusal to eat, and vomiting.
Here is a link to more information about the genetics of Arginase Deficiency that was prepared by our genetic counselor and which has links to some useful resources for those dealing with this condition: http://www.accessdna.com/condition/Arginase_Deficiency/42. There is also a phone number listed if you need to speak to a genetic counselor by phone. I hope it helps. Thanks, AccessDNA
Here is a link to more information about the genetics of Arginase Deficiency that was prepared by our genetic counselor and which has links to some useful resource for those dealing with this condition: http://www.accessdna.com/condition/Arginase_Deficiency/42. There is also a number listed for anyone who wants to speak to a genetic counselor by phone. I hope it helps. Thanks, AccessDNA
Post a Comment