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GTR Home > Conditions/Phenotypes > Citrullinemia type I

Citrullinemia type I

Synonyms
ASS deficiency; Citrullinemia 1; Classic citrullinemia; argininosuccinate synthetase deficiency
Modes of inheritance
Autosomal recessive inheritance (Orphanet)

Summary

Excerpted from the GeneReview: Citrullinemia Type I
Citrullinemia type I (CTLN1) presents as a spectrum that includes a neonatal acute form (the "classic" form), a milder late-onset form (the "non-classic" form), a form in which women have onset of symptoms at pregnancy or post partum, and a form without symptoms or hyperammonemia. Distinction between the forms is based primarily on clinical findings, although emerging evidence suggests that measurement of residual argininosuccinate synthase enzyme activity may help to predict those who are likely to have a severe phenotype and those who are likely to have an attenuated phenotype. Infants with the acute neonatal form appear normal at birth. Shortly thereafter, they develop hyperammonemia and become progressively lethargic, feed poorly, often vomit, and may develop signs of increased intracranial pressure (ICP). Without prompt intervention, hyperammonemia and the accumulation of other toxic metabolites (e.g., glutamine) result in increased ICP, increased neuromuscular tone, spasticity, ankle clonus, seizures, loss of consciousness, and death. Children with the severe form who are treated promptly may survive for an indeterminate period of time, but usually with significant neurologic deficits. Even with chronic protein restriction and scavenger therapy, long-term complications such as liver failure and other (rarely reported) organ system manifestations are possible. The late-onset form may be milder than that seen in the acute neonatal form, but commences later in life for reasons that are not completely understood. The episodes of hyperammonemia are similar to those seen in the acute neonatal form, but the initial neurologic findings may be more subtle because of the older age of the affected individuals. Women with onset of severe symptoms including acute hepatic decompensation during pregnancy or in the postpartum period have been reported. Furthermore, previously asymptomatic and non-pregnant individuals have been described who remained asymptomatic up to at least age ten years, with the possibility that they could remain asymptomatic lifelong.
Full text of GeneReview (by section):
Summary
Diagnosis
Clinical Characteristics
Genetically Related (Allelic) Disorders
Differential Diagnosis
Management
Genetic Counseling
Resources
Molecular Genetics
Chapter Notes
References
Authors:
Shane C Quinonez
Kristen N Lee
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Available tests

80 tests are in the database for this condition.

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Clinical tests (80 available)

Biochemical Genetics Tests

Molecular Genetics Tests

Genes See tests for all associated and related genes

  • Also known as: ASS, CTLN1, ASS1
    Summary: argininosuccinate synthase 1

Clinical features

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Imported from Human Phenotype Ontology (HPO)

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Reviews

Clinical resources

Practice guidelines

  • ACMG, ACT Sheet, 2022
    American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, [Elevated Citrulline], Amino Acidemia/Urea Cycle Disorder, 2022
  • ACMG Algorithm, 2022
    American College of Medical Genetics and Genomics, Elevated Citrulline: Amino Acidemia Algorithm, 2022
  • ACMG ACT, 2012
    American College of Medical Genetics and Genomics, Transition to Adult Health Care ACT Sheet, Citrullinemia I, Urea Cycle Disorder, 2012

Molecular resources

Consumer resources

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