Ornithine Transcarbamylase Deficiency
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What is ornithine transcarbamylase deficiency?
Ornithine transcarbamylase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.
Ornithine transcarbamylase deficiency often becomes evident in the first few days of life. An infant with ornithine transcarbamylase deficiency may be lacking in energy (lethargic) or unwilling to eat, and have poorly-controlled breathing rate or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Complications from ornithine transcarbamylase deficiency may include developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen.
In some affected individuals, signs and symptoms of ornithine transcarbamylase may be less severe, and may not appear until later in life.
How common is ornithine transcarbamylase deficiency?
Ornithine transcarbamylase deficiency is believed to occur in approximately 1 in every 80,000 people.
What genes are related to ornithine transcarbamylase deficiency?
Mutations in the OTC gene cause ornithine transcarbamylase deficiency.
Ornithine transcarbamylase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. It processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.
In ornithine transcarbamylase deficiency, the enzyme that starts a specific reaction within the urea cycle is damaged or missing. The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia.
Ammonia is especially damaging to the nervous system, so ornithine transcarbamylase deficiency causes neurological problems as well as eventual damage to the liver.
How do people inherit ornithine transcarbamylase deficiency?
Ornithine transcarbamylase deficiency is an X-linked disorder. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), mutations in both copies of the gene will cause the disorder. Some females with only one altered copy of the OTC gene also show signs and symptoms of ornithine transcarbamylase deficiency.
Source: National Institutes of Health
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Investigators at University of Porto, Institute of Pathology publish new data on life sciences
2009 JUN 16 - (NewsRx.com) -- Research findings, 'Molecular mechanisms underlying large genomic deletions in ornithine transcarbamylase (OTC) gene,' are discussed in a new report. According to recent research from Porto, Portugal, "Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle error causing hyperammonemia and orotic aciduria. Clinical diagnosis is generally confirmed by mutation detection." "However, in approximately 20% of the patients, no mutation is found by conventional mutation-searching strategies, which fail to detect deletions spanning at least a whole exon, large rearrangements, or mutations at non-coding regions. To detect large deletions or duplications, we have applied the multiplex ligation-dependent probe amplification (MLPA) methodology to three OTCD patients (two females and one male). MLPA revealed copy number alterations of OTC exons in all of them. The two females were found to be heterozygous for deletions of either exon 2 or exons 6-9, and the male was confirmed to lack all OTC exons. Females' characterization of the deletion breakpoints by long polymerase chain reaction and sequencing revealed the mutations c.78-3544_217-129del5921 and c.541-600_1005 + 1880del10862 corresponding to exon 2 and exon 6-9 deletions, respectively. Examination of the deletion-flanking regions suggests that exon 2 deletion probably resulted from replication slippage facilitated by a secondary structure formed by two inverted Alu repeats, whereas an Alu-Alu homologous recombination was probably responsible for the exon 6-9 deletion," wrote R. Quental and colleagues, University of Porto, Institute of Pathology. The researchers concluded: "This work contributes to the identification of novel disease-causing mutations in OTCD and increases the knowledge on possible mutational mechanisms generating deletions in OTC." Quental and colleagues published their study in Clinical Genetics (Molecular mechanisms underlying large genomic deletions in ornithine transcarbamylase (OTC) gene. Clinical Genetics, 2009;75(5):457-64). For additional information, contact R. Quental, IPATIMUP - Institute of Pathology and Molecular Immunology of University of Porto, Porto, Portugal. Publisher contact information for the journal Clinical Genetics is: Blackwell Publishing Inc., 350 Main St., Malden, MA 02148, USA. Keywords: Portugal, Porto, Life Sciences, Hyperammonemia, Pathology. This article was prepared by Science Letter editors from staff and other reports. Copyright 2009, Science Letter via NewsRx.com.
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