Description, Causes and Risk Factors:
A disorder of urea cycle due to a deficiency of argininosuccinate lyase (AL); characterized by physical and mental retardation, epilepsy, ataxia, liver disease, friable, tufted hair, and excessive urinary excretion of argininosuccinic acid (ASA). Autosomal recessive inheritance, caused by mutation in argininosuccinate lyase gene on chromosome 7q.
Argininosuccinate lyase (AL) has several roles in intermediary metabolism. It is an essential component of the urea cycle, providing a pathway for the disposal of excess nitrogen in mammals. AL links the urea cycle to the tricarboxylic acid (TCA) cycle by generating fumarate. Finally, AL is required for the endogenous production of arginine. In this latter role it may function outside ureagenic organs to provide arginine as a substrate for nitric oxide synthases (NOS). Increasing evidence suggests that argininosuccinate synthetase (ASS) and AL are more globally expressed, and the coordinate regulation of ASS and AL gene expression with that of the inducible form of NOS (i-NOS) provides evidence that this may facilitate the regulation of NOS activity. De?ciency of AL leads to the human urea cycle disorder argininosuccinicaciduria.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
If both members of a couple are carriers, the risk for an affected child is 25% in each pregnancy; therefore, it is especially important that the reproductive partner of a carrier be offered testing.
Argininosuccinicaciduria can occur in individuals of all races and ethnicities. It is estimated to affect 1 in 70,000 live births, with a calculated carrier frequency of 1 in 132.
Symptoms of argininosuccinicaciduria include:
Loss of appetite.
Poorly controlled body temperature.
Diagnosis is made by the existence of hyperammonemia and by chromatography of plasmatic and urinary organic acids that shows accumulation of argininosuccinic acid (ASA).Prenatal diagnosis is possible with enzyme assay of CVS or amniocytes.
No routine laboratory data assist diagnosis of argininosuccinicaciduria.Blood urea nitrogen (BUN) testing is subject to numerous factors aside from the rate of production via the urea cycle. Among the most obvious is the state of hydration, which frequently causes an artifactual increase to a normal concentration in a very sick infant.
A very low BUN level is suggestive but must never be relied on as a diagnostic indicator.
As with all other urea cycle disorders, clinical suspicion is essential and should prompt the clinician to obtain blood ammonia levels, which are significantly elevated in symptomatic patients. This finding should lead to an immediate blood and urine amino acid quantitation, which confirms the presence of argininosuccinic acid in both fluids. In addition, levels of blood citrulline, glutamine, alanine, and lysine may be increased. Argininosuccinic acid lyase may be assayed in cultured fibroblasts, providing the definitive biochemical diagnosis. Urine orotic acid levels are elevated.
Treatment consists of a low protein diet, arginine supplementation to help complete the urea cycle, ammonia scavenging drugs in some cases and supplement carnitine if the patients have a secondary deficiency. Liver transplant offers a partial correction of the enzyme deficiency and improved metabolic status. Patients must avoid fasting and during stressors, like illness, need to supplement with high carbohydrates, non-protein calories to avoid catabolism. In metabolic emergency, acute hemodialysis may be necessary to lower ammonia levels.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.
A new study from Brazil suggests that trendy intermittent fasting may be the reason for increasing insulin levels and the amount of abdominal fat. It also may lead to the damage of pancreatic cells. Intermittent fasting diet is a diet when a dieting person has “fast”...
It is well known that our overall health and wellbeing are totally dependable on what we eat. That is why a healthy diet plays a significant role in keeping the body healthy. Day after day, scientists all over the world make new discoveries proving that certain...
Quiz about this article
0 of 2 questions completed
Please answer on few questions to make our service more useful
You have already completed the quiz before. Hence you can not start it again.
Quiz is loading...
You must sign in or sign up to start the quiz.
You have to finish following quiz, to start this quiz:
0 of 2 questions answered correctly
Time has elapsed
You have reached 0 of 0 points, (0)
Question 1 of 2
Was this article useful for you?Correct
Thanks for your feedback!Incorrect
Thanks for your feedback!
Question 2 of 2
What else information about this disease you want to know ?Correct
Thanks for feedback!Incorrect
Thanks for feedback!
Good weather is the best reason to do outdoor sports, which will help not only lose weight, but also will strengthen health. Bicycle The sun dries out the local paths, so you can safely sit on your favorite bike and confidently twist the pedals, where the eyes look....read more
First aid for injuries consists of simple rules that need to be clearly implemented. If this is a closed injury, you need to immobilize the injured limb, otherwise the person may lose consciousness from a painful shock. If you need to get to the emergency room...read more
Many people spontaneously decide starting to do sport, while others weigh all the pros and cons for a log time. But almost all of them make the same mistakes, listening to the advice of non experts. There are 10 anti-tips for those who want to do plan to do some sport...read more