Citrullinemia
Classifications and external resources

Citrulline
ICD-10	E72.2
ICD-9	270.6
OMIM	215700 605814 603471
DiseasesDB	29676 34048
eMedicine	ped/406
MeSH	C10.228.140.163.100.175

Citrullinemia is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. Two forms of citrullinemia have been described; they have different signs and symptoms and are caused by mutations in different genes. Citrullinemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of chemical reactions that takes place in the liver. These reactions process excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys. Image File history File links Citrulline. ... The chemical compound citrulline is an α-amino acid (AA). ... The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) is a detailed description of known diseases and injuries. ... The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... // E00-E35 - Endocrine diseases (E00-E07) Disorders of thyroid gland (E00) Congenital iodine-deficiency syndrome (E01) Iodine-deficiency-related thyroid disorders and allied conditions (E02) Subclinical iodine-deficiency hypothyroidism (E03) Other hypothyroidism (E030) Congenital hypothyroidism with diffuse goitre (E031) Congenital hypothyroidism without goitre (E032) Hypothyroidism due to medicaments and other... The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) is a detailed description of known diseases and injuries. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Diseases Database is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... Ammonia is a compound of nitrogen and hydrogen with the formula NH3. ... Human blood smear: a - erythrocytes; b - neutrophil; c - eosinophil; d - lymphocyte. ... The Urea Cycle is a cycle of biochemical reactions occurring in many animal organisms that produces urea from ammonia. ... The liver is the largest internal organ of the human body. ... General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless Atomic mass 14. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Human kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ...

Both types of citrullinemia are inherited in an autosomal recessive pattern. In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ...

Types

Type I

Type I citrullinemia (Mendelian Inheritance in Man (OMIM) 215700, also known as classic citrullinemia) usually becomes evident in the first few days of life. Affected infants typically appear normal at birth, but as ammonia builds up in the body they develop a lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. These medical problems can be life-threatening in many cases. Less commonly, a milder form of type I citrullinemia can occur in childhood or adulthood. Some people with gene mutations that cause type I citrullinemia never experience signs and symptoms of the disorder. The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... Fatigue is a feeling of excessive tiredness or lethargy, with a desire to rest, perhaps to sleep. ... Vomiting (or emesis) is the forceful expulsion of the contents of ones stomach through the mouth. ... This article is about the medical term, epileptic seizure, as distinct from psychogenic non-epileptic seizure. ...

Type I citrullinemia is the most common form of the disorder, affecting about 1 in 57,000 births worldwide. Mutations in the ASS gene cause type I citrullinemia. The enzyme made by this gene, argininosuccinate synthetase (EC 6.3.4.5), is responsible for one step of the urea cycle. Mutations in the ASS gene reduce the activity of the enzyme, which disrupts the urea cycle and prevents the body from processing nitrogen effectively. Excess nitrogen, in the form of ammonia, and other byproducts of the urea cycle accumulate in the bloodstream, leading to the characteristic features of type I citrullinemia. In biology, mutations are changes to the genetic material (either DNA or RNA). ... ASS (argininosuccinate synthetase) is a human gene that provides instructions for making an enzyme called argininosuccinate synthetase. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Argininosuccinate synthetase is an enzyme that participates in the urea cycle, which is a sequence of chemical reactions that takes place in the cells of the liver. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ...

Type II

The signs and symptoms of type II citrullinemia (Mendelian Inheritance in Man (OMIM) 605814 and Mendelian Inheritance in Man (OMIM) 603471) usually appear during adulthood and mainly affect the nervous system. Characteristic features include confusion, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma. These signs and symptoms can be life-threatening, and are known to be triggered by certain medications, infections, and alcohol intake in people with type II citrullinemia. The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The nervous system of an animal coordinates the activity of the muscles, monitors the organs, constructs and also stops input from the senses, and initiates actions. ... In chemistry, an alcohol is any organic compound in which a hydroxyl group (-OH) is bound to a carbon atom of an alkyl or substituted alkyl group. ...

Type II citrullinemia may also develop in people who had a liver disorder called neonatal intrahepatic cholestasis during infancy. This condition blocks the flow of bile and prevents the body from processing certain nutrients properly. In many cases, the signs and symptoms resolve within a year. Years or even decades later, however, some of these people develop the characteristic features of adult type II citrullinemia. The liver is the largest internal organ of the human body. ... Bile (or gall) is a bitter, greenish-yellow alkaline fluid secreted by the liver of most vertebrates. ...

Type II citrullinemia is primarily found in the Japanese population, where it occurs in an estimated 1 in 100,000 to 230,000 individuals. Type II has also been reported in people from East Asian and Middle Eastern populations. Mutations in the SLC25A13 gene are responsible for type II citrullinemia. This gene makes a protein called citrin, which normally shuttles certain molecules in and out of mitochondria. These molecules are essential for the urea cycle and are also involved in making proteins and nucleotides. Mutations in the SLC25A13 mutation typically prevent the production of any functional citrin, which inhibits the urea cycle and disrupts the production of proteins and nucleotides. The resulting buildup of ammonia and other toxic substances leads to the signs and symptoms of type II citrullinemia. Researchers have determined that many infants with neonatal intrahepatic cholestasis have the same mutations in the SLC25A13 gene as adults with type II citrullinemia. East Asia is a subregion of Asia that can be defined in either geographical or cultural terms. ... A map showing countries commonly considered to be part of the Middle East The Middle East is a region comprising the lands around the southern and eastern parts of the Mediterranean Sea, a territory that extends from the eastern Mediterranean Sea to the Persian Gulf. ... In cell biology, a mitochondrion is an organelle found in the cells of most eukaryotes. ... A nucleotide is a chemical compound that consists of a heterocyclic base, a sugar, and one or more phosphate groups. ...

See also

• Hyperammonemia

Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. ...

External links

• Citrullinemia - Geneva Foundation for Medical Education and Research
• The U.S. National Library of Medicine (This article incorporates public domain text from this source)