Citrullinemia I or type 1 (classic form)
Citrullinemia type II
Argininosuccinate synthetase deficiency (AS or ASS)
Argininosuccinic acid synthetase deficiency (ASAS)
Initial symptoms may include:
- poor appetite
- increased intracranial pressure
- coma, possibly leading to death and
- lab findings:
- elevated citrulline and glutamine
- absent argininosuccinic acid
Symptoms of the milder form in children may include:
- poor growth
- poor appetite
- learning disabilities
- behavior problems
- balance and coordination problems, and
Symptoms of citrullinemia in aduts may include:
- Psychotic changes
- Acute liver failure
Therapy consists in protein restriction, the administration of arginine supplements and nitrogen scavengers (phenylbutyrate, phenylacetate, benzoate) in citrullinemia type 1. By contrast, a diet low in carbohydrates is indicated in citrullinemia type 2.
- Contact the family and evaluate the infant for poor feeding, vomiting, lethargy, tachypnea;
- Provide emergency treatment/referral for symptoms of vomiting, hypotonia, tachypnea, seizures, or signs of liver disease (see the ACT Sheet for Elevated Citrulline (ACMG) ( 346 KB) for additional information);
- To confirm the diagnosis, work with the following service(s): see all Newborn Screening Programs services providers (3) in our database;
- For evaluation and ongoing collaborative management, consult the following service(s): Pediatric Medical Genetics , (801-213-3599); See also Services below;
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Citrullinemia - Information for Parents (STAR-G));
- Assist in implementation and maintenance of a low protein diet, provision of arginine and essential amino acid supplements, and therapy with sodium phenylbutyrate;
- Regular blood tests to monitor amino acid and ammonia levels may be indicated;
- Sodium benzoate and/or phenylburtyrate/phenylacetate and arginine to manage hyperammonemic crises or dialysis may be indicated;
- For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.
Citrullinemia - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.
ACT Sheet for Elevated Citrulline (ACMG) ( 346 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.
Newborn Screening ACT Sheets & Confirmatory Algorithms (ACMG)
ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results, membership required; American College of Medical Genetics.
Neonatal Hyperammonemia Emergency Protocol (NECMP)
A guideline for health care professionals treating the sick neonate with hyperammonemia; developed under the direction of Dr. Harvey Levy, Senior Associate in Medicine/Genetics at Children’s Hospital Boston, and Professor of Pediatrics at Harvard Medical School, for the New England Consortium of Metabolic Programs.
Infant/Child Hyperammonemia Acute Illness Protocol (NECMP) ( 57 KB)
A guideline for health care professionals treating the sick infant/child who has previously been diagnosed with citullinemia; developed under the direction of Dr. Harvey Levy, Senior Associate in Medicine/Genetics at Children’s Hospital Boston, and Professor of Pediatrics at Harvard Medical School, for the New England Consortium of Metabolic Programs.
Excellent review by Jess G Thoene, MD including clinical description, differential, management, genetic counseling, molecular genetics, and a bibliography.
Resources for Citrullinemia (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.
Utah Newborn Screening Program (UDOH)
Provides information about the program, related legislation, training for practices, and newborn conditions; Utah Department of Health.
Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.
Citrullinemia - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.
Citrullinemia (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; U.S. National Library of Medicine.
National Urea Cycle Disorders Foundation
This non-profit organization provides support services and information for families; medical lectures on urea cycle disorders; nutrition and medication resources; and information about events and conferences.
Newborn Screening Information for Clinicians (NNSGRC)
Fact sheets, data reports, publications ,and information for clinicians about genetic screening that includes links to state genetic contacts; National Newborn Screening & Global Resource Center.
See all Newborn Screening Programs services providers (3) in our database.
See all Pediatric Genetics services providers (5) in our database.
For other services related to this condition, browse our Services categories or search our database.
|Content Last Updated:||6/2012|
Saheki T, Inoue K, Tushima A, Mutoh K, Kobayashi K.
Citrin deficiency and current treatment concepts.
Mol Genet Metab. 2010;100 Suppl 1:S59-64. PubMed abstract
The historical aspects of citrin and citrin deficiency and current treatment concepts for citrin deficiency are described. Developing novel therapeutics based on the pathophysiology, such as sodium pyruvate, are discussed.
Salek J, Byrne J, Box T, Longo N, Sussman N.
Recurrent liver failure in a 25-year-old female.
Liver Transpl. 2010;16(9):1049-53. PubMed abstract
Urea cycle defects such as Citrullinemia type I are not generally considered causes of ALF in adults and are described rarely in children beyond the neonatal period. Prompt diagnosis and treatment can enable the patient to recover fully.
Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.
Pediatrics. 2003;111(6 Pt 1):1399-406. PubMed abstract