, also called arginase deficiency
, is an autosomal recessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
urea cycle disorder
An urea cycle disorder or urea cycle defect is a genetic disorder caused by a deficiency of one of the enzymes in the urea cycle which is responsible for removing ammonia from the blood stream. The urea cycle involves a series of biochemical steps in which nitrogen, a waste product of protein...
where a deficiency of the enzyme arginase
Arginase is a manganese-containing enzyme. The reaction catalyzed by this enzyme is: arginine + H2O → ornithine + urea. It is the final enzyme of the urea cycle.- Structure and function :Arginase belong to the ureohydrolase family of enzymes....
causes a build up of arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
in the blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.
Argininemia usually becomes evident by about the age of 3. It most often appears as stiffness, especially in the legs, caused by abnormal tensing of the muscles (spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
). Other symptoms may include slower than normal growth, developmental delay and eventual loss of developmental milestones, mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, seizures, tremor, and difficulty with balance and coordination (ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
). Occasionally, high protein meals or stress caused by illness or periods without food (fasting) may cause ammonia to accumulate more quickly in the blood. This rapid increase in ammonia may lead to episodes of irritability, refusal to eat, and vomiting.
In some affected individuals, signs and symptoms of argininemia may be less severe, and may not appear until later in life.
Mutations in the ARG1
gene cause argininemia.
Argininemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle
The urea cycle is a cycle of biochemical reactions occurring in many animals that produces urea from ammonia . This cycle was the first metabolic cycle discovered , five years before the discovery of the TCA cycle...
is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.
gene provides instructions for making an enzyme called arginase. This enzyme controls the final step of the urea cycle, which produces urea by removing nitrogen from arginine. In people with arginase deficiency, arginase is damaged or missing, and arginine is not broken down properly. As a result, urea cannot be produced normally, and excess nitrogen accumulates in the blood in the form of ammonia. The accumulation of ammonia and arginine are believed to cause the neurological problems and other signs and symptoms of arginase deficiency.
The accumulation of guanidino metabolites also contribute to the neurotoxicity of the disease.
This condition is an autosomal recessive disorder, which means the defective gene is located on an autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
, and two copies of the defective gene are required to inherit the disorder. Both parents of an individual with an autosomal recessive disorder are carriers of one copy of the gene, but usually do not have the disorder.