Carbamyl phosphate synthetase I, ... deficiency; Congenital hyperammonemia type I (Carbamoyl phosphate synthetase I deficiency, congenital hyperammonemia type I) - Gen CPS1

Deficiency carbamyl phosphate synthetase I, also known as congenital hyperammonemia type I or CPS1 deficiency is a hereditary disorder which results in an accumulation of blood ammonia (hyperammonemia). Ammonia, which is formed when proteins are broken down in the body, is toxic at high concentrations. The brain is particularly sensitive to excess ammonia.

In the early days of life, newborns with deficiency of carbamyl phosphate synthetase I usually show symptoms of hyperammonemia. These symptoms may include drowsiness, respiratory rate or dysregulated body temperature, loss of appetite, vomiting after feeding, unusual body movements, seizures, or coma. Affected individuals who survive the neonatal period may suffer recurrent episodes of these symptoms to inadequate or have infections or other stressors diet. In addition, they may show developmental delay and intellectual disability. In some affected individuals, signs and symptoms may be less severe and appear later in life.

This process is due to mutations in the CPS1 gene (carbamoyl-phosphate synthase 1), located on the long arm of chromosome 2 (2q35), encoding the enzyme carbamyl phosphate synthetase I. This enzyme participates in the urea cycle, one series of metabolic reactions occurring in the liver cells to remove excess nitrogen generated when proteins are used by the body. Excrete excess nitrogen prevents the buildup nitrogen as ammonia, since it is toxic in excessive concentrations.

They have identified at least 245 mutations in the gene responsible for CPS1 carbamyl phosphate synthetase deficiency I. These mutations correspond to: missense mutations (162), and cutting mutations -splicing- junction (23), small deletions (31) , small insertions (14), small insertions / deletions (4), larger deletions (10) and insertions / higher duplications (1). A mutated gene can result CPS1 an enzyme carbamyl phosphate synthetase I which is shorter than normal or incorrectly, or can completely inhibit the synthesis of carbamyl phosphate synthetase I. form of an enzyme affects its ability regulate a chemical reaction. If the enzyme carbamyl phosphate synthetase I is deformed or absent, it can not play its role in the urea cycle. As a result, the excess nitrogen is not converted into urea for excretion and ammonia accumulates in the body.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with carbamyl phosphate synthetase deficiency type I, by complete PCR amplification of the exons of the gene CPS1 and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).