Ornithine Transcarbamylase Deficiency

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Ornithine Transcarbamylase Deficiency

Ornithine Transcarbamylase Deficiency


Ornithine transcarbamylase deficiency is a very common enzyme deficiency transmitted a recessive or X-linked dominant. In girls, the severity of the disease varies widely depending on the degree of inactivation of the X gene. The complete enzyme deficiencies are always expressed in males, hemizygous for neonatal hyperammonemic coma very serious, often fatal.


OTC is an X-linked gene encoding a critical enzyme in the urea cycle. Inactivating mutations lead to early lethality in males, while less severe mutations cause various degrees of health defects. Interestingly, although germline mutations are carried by heterozygous females, a significant number of carriers show clinical symptoms including lethality. Most of the clinical symptoms can be attributed to hyperammonemia (Baltimore, 2006). Ammonia has long been known as a lysosomotropic inhibitor in vitro. It can prevent the fusion of the endosomes and lysosomes. Proper function of the lysosome is essential to the presentation of antigens of APCs to T cells through the MHC II and CD1d pathways. In vitro, it has been shown that ammonia inhibits MHC II presentation. It is therefore of great interest to determine whether OTC mutation affects immune function. Spare fur (spf) mice have a spontaneous mutation (His117>Asn) of the Otc gene, which results in a marked decrease in the enzyme activity under physiological condition. While mutant hemizygous male mice have significantly shortened life spans, the female carriers have a fairly normal life span and are fertile. Since the spf mutation results in hyperammonemia, it offered a valuable model to explore potential immune defects associated with abnormal nitrogen waste clearance. Here we show that despite absence of Otc expression in the thymus, the mutation of OTC selectively impairs MHC class II expression in thymic epithelial cells, which causes inefficient deletion of autoreactive T cells and production of regulatory T cells in the thymus; the mutation also impairs the presentation of endogenous NKT ligand on thymocytes, which leads to less NKT cells produced in the thymus (Philip, 2007).

Once the diagnosis of OTC deficiency was established in a family, it is necessary to investigate the family history and perform detailed search for possible female carriers. If the mutation is identified, is this the best way for investigation. Of not having this information, more convenient for some authors is the test of allopurinol, which appears to have high sensitivity and specificity. For other authors, is a method that may have errors? Symptomatic carriers should initiate treatment (Gene, 2006). In all cases the carriers (symptomatic and not symptomatic) should be warned of a possible imbalance in the immediate postpartum period. An estimated 15% of carrier females have hyperammonemia at some point in their lives. In the family presented, has not yet been possible to begin the search for carriers.


Ornithine transcarbamoylase (OTCase, EC catalyzes the following reaction:

OTCase is widely distributed throughout the phylogenetic spectrum. Eukaryotes and most bacteria possess anabolic OTCase. In prokazyotes (Cunin etol., 1986) and fungi (Eisenstein et a!., 1984), anabolic OTCaSC functions in arginine biosynthesis; in plants it serves ...
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