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Citrullinemia type I


Other Names for this Disease

  • Argininosuccinate synthetase deficiency
  • ASS deficiency
  • Citrullinemia 1
  • Citrullinuria
  • Classic citrullinemia
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Overview

What is citrullinemia type I?

What are the symptoms of citrullinemia type I?

What causes citrullinemia type I?

How is citrullinemia type I inherited?

What is citrullinemia type I?

Citrullinemia type I is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. This condition, also known as classic citrullinemia, belongs to a class of genetic diseases called urea cycle disorders.[1] In most cases, the condition 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 experience a progressive lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness.[1][2] Citrullinemia type I is caused by mutations in the ASS1 gene. It is inherited in an autosomal recessive pattern.[1]
Last updated: 4/20/2010

What are the symptoms of citrullinemia type I?

Citrullinemia type I presents as a clinical spectrum that includes an acute neonatal form, a milder late-onset form, a form without symptoms and/or hyperammonemia, and a form in which women have onset of severe symptoms during pregnancy or post partum.[3] Infants with the acute neonatal form typically appear normal at birth, but as ammonia builds up in the body they become progressively lethargic, feed poorly, vomit, and develop signs of increased intracranial pressure, which can lead to seizures and loss of consciousness.[1][3] Less commonly, a milder form of citrullinemia type I can develop later in childhood or adulthood. This later-onset form is associated with intense headaches, partial loss of vision, slurred speech, problems with balance and muscle coordination (ataxia), behavior problems, and lethargy.[1][4] Episodes of high blood ammonia often happen after going without food for long periods of time, during illness or infection or after high-protein meals.[4] Some people with gene mutations that cause citrullinemia type I never experience signs and symptoms of the disorder and are only found to be affected after a brother or sister is diagnosed.[1][4]
Last updated: 4/20/2010

What causes citrullinemia type I?

Citrullinemia type I is caused by mutations in the ASS1 gene.[1] This gene provides instructions for making an enzyme, argininosuccinate synthetase 1, that is responsible for the third step in the urea cycle.[1][3] Mutations in the ASS1 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. Ammonia is particularly toxic to the nervous system, which helps explain the neurologic symptoms (such as lethargy, seizures, and ataxia) that are often seen in this condition.[1]
Last updated: 4/20/2010

How is citrullinemia type I inherited?

Citrullinemia type I is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.[1]
Last updated: 4/20/2010

References
  1. Citrullinemia. Genetics Home Reference (GHR). 2006; http://www.ghr.nlm.nih.gov/condition=citrullinemia. Accessed 7/11/2011.
  2. Citrullinemia. National Organization for Rare Disorders (NORD). 2001; http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Citrullinemia. Accessed 4/20/2010.
  3. Thoene JG. Citrullinemia Type I. GeneReviews. 2009; http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ctlm. Accessed 4/20/2010.
  4. Citrullinemia. Screening, Technology and Research in Genetics (STAR-G). 2007; http://www.newbornscreening.info/Parents/aminoaciddisorders/ASAS.html. Accessed 4/20/2010.


Other Names for this Disease
  • Argininosuccinate synthetase deficiency
  • ASS deficiency
  • Citrullinemia 1
  • Citrullinuria
  • Classic citrullinemia
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.