If science were art and art were science, then the howling black wolf has probably swallowed some N-(4-hydroxyphenyl)ethanamide.
Ornithine Transcarbamylase Deficiency (OTCD) is another rare, genetic, metabolic disorder that involves a defect in urea cycle. Although it only occurs in one out of 80 000 births, it is the most common form of urea metabolic disorder. An X-linked, recessive disorder, OTCD involves the failure of the body to properly process ammonia. When left untreated, OTCD may lead to coma and, subsequently, death.
Protein and amino acid metabolism naturally generates waste nitrogen in the form of ammonia. Because too much it is toxic for the body, the generated ammonia is excreted in the form of urea through the urea or ornithine cycle. It occurs mostly in the liver and, in a lesser extent, kidneys. Described by Hans Krebs and Kurt Henseleit, it was the first metabolic cycle discovered. It involves both the mitochondria and other hepatic tissues.
In patients with OCTD, there is a failure to incorporate citrulline with ornithine by condensation. This results to an increase in hepatic ornithine as reflected in the elevated serum level. Furthermore, an excess of mitochondrial carbamyl phosphate leaks out into the cytosol. Acting as substrate for the carbomoyl phosphate synthetase (CPS) II reaction, orotic acid is produced. Because of this, diminished ornithine transport into mitochondria occurs. This is followed ornithine accumulation in the cytoplasm which reduces the ability to clear carbamoyl phosphate and ammonia loads.
Mutation of the X chromosome at band p21.1 causes OTCD. The gene spans more than 85 kb and is comprised of 10 exons encoding a protein of 1062 amino acids. Because OTCD is a recessive disorder, the mutated gene must be inherited both from the mother and father in order to have the condition.
The symptoms present several days after an infant is born. Periods of inactivity and lack of energy and unwillingness to eat are observed. Seizures. enlarged liver, and unusual body movements may also be present. More importantly, hyperammonemia, excess of ammonia in blood, is the most common and defining symptom. Hyperammonemia is manifested by episodic attacks such as vomiting, lack of apetie, drowsiness, hepatomegaly, seizures, coma and death.
On the other hand, patients with a milder form of OTCD only exhibit developmental delay. Others experience nausea succeeding a heavy-protein meal.
Treament and Management
Severely affected individuals are advised to undergo liver transplants. On the other hand, patients that are less severely affected or those that cannot afford to have transplants undergo long-term treatment. It includes decrease in nitrogen-intake (low-protein diet), prevention of excessive protein breakdown (diet and nutrition), and intravenous administration of sodium benzoate and sodium phenylacetate (nitrogen scavengers). Supplemental amino acids like arginine, citrulline, valine, and leucine are also prescribed.
*OTCD was featured in episode 15, season 1 of the medical series House, M.D. .