Get Help in New MexicoCitrullinemia Type 1
Guidance for primary care clinicians receiving a positive newborn screen result
Description
Citrullinemia results from a deficiency of argininosuccinate synthetase (ASS), disrupting the 3rd step of the urea cycle, the pathway that converts ammonia to urea. Clinical manifestations are highly variable with a neonatal form of the condition typically presenting in the first few days of life with lethargy, poor feeding, and vomiting secondary to hyperammonemia. In the late-onset non-classical form of citrullinemia, symptoms that are typically milder can develop any time from infancy to adulthood. Recurrent episodes of metabolic decompensation and hyperammonemia are triggered by catabolism (due to fasting or illnesses) or excess protein intake. Treatment is available with strict dietary changes and nitrogen scavenging medications.
Clinical Characteristics
Without treatment, citrullinemia type I characteristically presents with neonatal-onset hyperammonemia along with associated complications of lethargy, poor feeding, and progressive neurological compromise. [Bachmann: 2003] This may be a metabolic emergency, so acute management under the supervision of a metabolic geneticist may be necessary if symptomatic. Less acute later-onset forms may present anytime from infancy to adulthood and are triggered by fasting, increased energy demands (fever, stress, lack of sleep), and excess protein intake. Women also may first experience symptoms in the postpartum period following pregnancy.
Initial neonatal symptoms may include:
- Poor appetite
- Vomiting
- Lethargy
- Seizures
- Coma
- Tachypnea
- Signs of liver disease
- Poor growth
- Vomiting
- Headaches/Migraines
- Learning disabilities
- Behavior problems
- Postpartum psychosis
- Hepatic dysfunction
Primary Care Management
Next Steps After a Positive Screen
- Contact the family and evaluate the infant for poor feeding, vomiting, lethargy, and tachypnea.
- Provide emergency treatment/referral for symptoms of vomiting, hypotonia, tachypnea, seizures, or signs of liver disease. Plasma ammonia and lactate levels may be indicated. See the ACT Sheet for Elevated Citrulline (ACMG).
Confirming the Diagnosis
- To confirm the diagnosis, work with Newborn Screening Services (see NM providers [3]).
- In affected individuals, plasma amino acids will identify the elevated citrulline level. However, there are other inborn errors of metabolism in which citrulline may be elevated and must be differentiated for management purposes. Urine amino acids may also be tested. An ammonia level should also be checked if symptomatic and/or the newborn screen positive predictive values are sufficiently high enough to suspect a true positive result. Genetic testing can confirm the diagnosis and differentiate the various disorders caused by elevated citrulline.
If the Diagnosis is Confirmed
- For evaluation and ongoing collaborative management, consult Medical Genetics (see NM providers [2]).
- 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 the maintenance of a low-protein diet, provision of arginine and essential amino acid supplements, and therapy with ammonia scavenger medications.
- Regular blood tests to monitor amino acid and ammonia levels may be indicated.
- For those identified after irreversible consequences, assist in management, particularly with developmental and educational resources. Refer as needed to Early Intervention for Children with Disabilities/Delays (see NM providers [34]).
Resources
Information & Support
After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive for
a newborn condition. Find information about A New Diagnosis - You Are Not Alone;
Caring for Children with Special Health Care Needs; Assistance in Choosing
Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a
Diagnosis.
For Professionals
Citrullinemia Type 1 (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular
pathogenesis; from the University of Washington and the National Library of Medicine.
Communicating Newborn Screening Results to Families (ACHDNC)
One-page guide to help clinicians effectively communicate positive newborn screening results to parents; Advisory Committee
on Heritable Disorders in Newborns and Children.
For Parents and Patients
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 (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources;
from the National Library of Medicine.
National Urea Cycle Disorders Foundation
Support and information that includes medical lectures on urea cycle disorders, nutrition and medication resources, and information
about events and conferences.
Tools
Confirmatory Algorithm for Citrulline Elevated (ACMG)
Graphical algorithm for responding to finding an elevated citrulline level on newborn screening; from the American College
of Medical Genetics and Genomics.
NM ACT Sheet for Elevated Citrulline (ACMG) (
117 KB)
Provides recommendations for clinical and laboratory follow-up of the newborn with out-of-range screening results, along with
national and local resources for clinicians and families; American College of Medical Genetics.
Services for Patients & Families in New Mexico (NM)
| Service Categories | # of providers* in: | NM | NW | Other states (3) (show) | | NV | RI | UT |
|---|---|---|---|---|---|---|---|---|
| Early Intervention for Children with Disabilities/Delays | 34 | 3 | 30 | 13 | 51 | |||
| Medical Genetics | 2 | 1 | 5 | 4 | 7 | |||
| Newborn Screening Services | 3 | 1 | 2 | 2 | 3 | |||
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
Page Bibliography
Bachmann C.
Outcome and survival of 88 patients with urea cycle disorders: a retrospective evaluation.
Eur J Pediatr.
2003;162(6):410-6.
PubMed abstract
Bourdeaux C, Darwish A, Jamart J, Tri TT, Janssen M, Lerut J, Otte JB, Sokal E, de Ville de Goyet J, Reding R.
Living-related versus deceased donor pediatric liver transplantation: a multivariate analysis of technical and immunological
complications in 235 recipients.
Am J Transplant.
2007;7(2):440-7.
PubMed abstract
Brusilow SW, Horwich AL.
The Metabolic & Molecular Bases of Inherited Diseases: Urea Cycle Enzymes (Chapter 85).
8 ed. Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B,;
2001.
Perito ER, Rhee S, Roberts JP, Rosenthal P.
Pediatric liver transplantation for urea cycle disorders and organic acidemias: United Network for Organ Sharing data for
2002-2012.
Liver Transpl.
2014;20(1):89-99.
PubMed abstract / Full Text
Summar ML, Koelker S, Freedenberg D, Le Mons C, Haberle J, Lee HS, Kirmse B.
The incidence of urea cycle disorders.
Mol Genet Metab.
2013;110(1-2):179-80.
PubMed abstract / Full Text