The CPS1 gene is located on chromosome 2q34. It encodes a mitochondrial enzyme called carbamoyl phosphate synthetase I. This enzyme comprises of 1,500 amino acids and weighs approximately 17 kDa. Carbamoyl phosphate synthetase I plays an important role in the urea cycle, which is important in the removal of excess urea from cells. It catalyzes synthesis of carbamoyl phosphate from ammonia and bicarbonate, which is the first committed step in the urea cycle to excrete the excess nitrogen from the body.
Defects in the carbamoyl phosphate synthetase I enzyme result in stopping the urea cycle; excess nitrogen will not be converted to urea for excretion, and ammonia will accumulate in the body causing neurological problems and other signs and symptoms of carbamoyl phosphate synthetase I deficiency. Symptoms include protein intolerance, intermittent ataxia, seizures, lethargy, developmental delay and mental retardation.
The CPS1 gene consists of 38 coding exons and is about 201 kb in length. It has three transcript variants encoding different isoforms. These variations influence the availability of precursors for nitric oxide (NO) synthesis and play a role in clinical situations where endogenous NO production is critically important, such as neonatal pulmonary hypertension, increased pulmonary artery pressure following surgical repair of congenital heart defects or hepatovenocclusive disease following bone marrow transplantation. Mutations in the CPS1 gene have been associated with carbamoyl phosphate synthetase I deficiency, susceptibility to persistent pulmonary hypertension, and susceptibility to venoocclusive disease after bone marrow transplantation. About 10 different mutations have been identified in patients carbamoyl phosphate synthetase I deficiency.
Al-Shamsi et al. (2014) undertook a study to calculate the birth prevalence of IEMs among Emiratis in the UAE by taking into consideration all neonates born with an inherited metabolic condition at Tawam Hospital between 1995 and 2012. Al-Shamsi et al. (2014) identified a previously reported c.1509dup (p.V531CfsX91) frameshift mutation in the CPS1 gene in an Emirati patient affected with CPS1 Deficiency.
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