Citrullinemia Follow-up

Author: Karl S Roth, MD; Chief Editor: Bruce Buehler, MD more...

Updated: Mar 13, 2012

What would you like to print?

Further Outpatient Care
Transfer
Deterrence/Prevention
Complications
Prognosis
Patient Education
Show All

Further Outpatient Care

Patients with citrullinemia must be under the ongoing care of a biochemical geneticist or metabolic disease specialist with expertise in the care of urea cycle disorders.

A trained nutritionist should monitor the low-protein diet, which is essential in treatment.

Frequent monitoring of growth and blood amino acid levels is imperative in order to make adjustments before essential amino acid levels fall below normal and the child becomes catabolic.

Under no circumstances should a primary care provider provide follow-up for a patient with citrullinemia without the frequent input of a specialist.

Transfer

Any infant or child noted to have hyperammonemia should be considered for transfer to a medical center for further evaluation.

Deterrence/Prevention

Prenatal diagnosis is possible and is available at academic centers. Molecular diagnosis is possible, using amniocytes or chorionic villi.

Complications

Complications are chiefly neurological, including mental retardation, acute hyperammonemic coma, and death.

Prognosis

Consistent with the course of most urea cycle disorders, the degree of intellectual impairment is roughly parallel to the severity of initial presentation and frequency of subsequent hyperammonemic episodes. Subsequent hyperammonemic episodes predictably recur with any intercurrent infection.

With appropriate treatment, survival into adulthood is possible and has been documented.

Patient Education

Both parents of an affected infant are assumed to be obligate heterozygotes because citrullinemia is an autosomal recessive trait; therefore, the recurrence rate in every subsequent pregnancy is 1 in 4, or 25%.

Genetic counseling is indicated.

Advise the parents to seek early medical care for the affected child at the earliest signs of infection.

Counsel the parents regarding strict adherence to the prescribed medical regimen.

Prenatal diagnosis is theoretically available, although it is not trivial.

Contributor Information and Disclosures

Author

Karl S Roth, MD Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Clinical Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Robert D Steiner, MD Credit Unions for Kids Professor of Pediatric Research, Professor of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Faculty, Program in Molecular and Cellular Biosciences, Oregon Health and Science University School of Medicine; Attending Physician, Doernbecher Children's Hospital; Staff Consultant, Director of Metabolic Bone Disease Clinic, Shriners Hospital Portland

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research

Disclosure: Amicus Honoraria Consulting; Actelion Honoraria Consulting; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Consulting; Genzyme Honoraria Consulting; Shire Honoraria Consulting

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Leonard G Feld, MD, PhD, MMM, FAAP Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center

Leonard G Feld, MD, PhD, MMM, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

Prestes CC, Sgaravatti AM, Pederzolli CD, et al. Citrulline and ammonia accumulating in citrullinemia reduces antioxidant capacity of rat brain in vitro. Metab Brain Dis. Mar 2006;21(1):63-74. [Medline].
Saheki T, Kobayashi K. Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD). J Hum Genet. 2002;47(7):333-41. [Medline].
Noto D, Takahashi K, Hamaguchi T, et al. A case of adult onset type II citrullinemia with portal-systemic shunt. J Neurol Sci. Mar 12 2009;[Medline].
Yazaki M, Ikeda S, Kobayashi K, Saheki T. Therapeutic approaches for patients with adult-onset type II citrullinemia (CTLN2): effectiveness of treatment with low-carbohydrate diet and sodium pyruvate. Rinsho Shinkeigaku. Nov 2010;50(11):844-7. [Medline].
Nakamura M, Yazaki M, Kobayashi Y, Fukushima K, Ikeda S, Kobayashi K, et al. The characteristics of food intake in patients with type II citrullinemia. J Nutr Sci Vitaminol (Tokyo). 2011;57(3):239-45. [Medline].
Engel K, Hohne W, Haberle J. Mutations and polymorphisms in the human argininosuccinate synthetase (ASS1) gene. Hum Mutat. Mar 2009;30(3):300-7. [Medline].
Marquis-Nicholson R, Glamuzina E, Prosser D, Wilson C, Love DR. Citrullinemia type I: molecular screening of the ASS1 gene by exonic sequencing and targeted mutation analysis. Genet Mol Res. Aug 3 2010;9(3):1483-9. [Medline].
Nagasaka H, Okano Y, Tsukahara H, et al. Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period. Mol Genet Metab. Jan 25 2009;[Medline].
Berry GT, Steiner RD. Long-term management of patients with urea cycle disorders. J Pediatr. Jan 2001;138(1 Pt 2):S56-S62. [Medline].
Hayakawa M, Kato Y, Takahashi R, Tauchi N. Case of citrullinemia diagnosed by DNA analysis: including prenatal genetic diagnosis from amniocytes of next pregnancy. Pediatr Int. Apr 2003;45(2):196-8. [Medline].
Issa AR, Yadav G, Teebi AS. Intrafamilial phenotypic variability in citrullinaemia: report of a family. J Inherit Metab Dis. 1988;11(3):306-7. [Medline].
Kennaway NG, Harwood PJ, Ramberg DA, Koler RD, Buist NR. Citrullinemia: enzymatic evidence for genetic heterogeneity. Pediatr Res. Jun 1975;9(6):554-8. [Medline].
Kuhara H, Wakabayashi T, Kishimoto H, et al. Neonatal type of argininosuccinate synthetase deficiency. Report of two cases with autopsy findings. Acta Pathol Jpn. Jul 1985;35(4):995-1006. [Medline].
Matsuda I, Anakura M, Arashima S, Saito Y, Oka Y. A variant form of citrullinemia. J Pediatr. May 1976;88(5):824-6. [Medline].
Morrow G 3rd, Barness LA, Efron ML. Citrullinemia with defective urea production. Pediatrics. Oct 1967;40(4):565-74. [Medline].
Ohura T, Kobayashi K, Tazawa Y, et al. Clinical pictures of 75 patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). J Inherit Metab Dis. Apr 2007;30(2):139-44. [Medline].
Saheki T, Kobayashi K, Iijima M, et al. Metabolic derangements in deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier. Hepatol Res. Oct 2005;33(2):181-4. [Medline].
Steiner RD, Cederbaum SD. Laboratory evaluation of urea cycle disorders. J Pediatr. Jan 2001;138(1 Suppl):S21-9. [Medline].
Tamamori A, Fujimoto A, Okano Y, et al. Effects of citrin deficiency in the perinatal period: feasibility of newborn mass screening for citrin deficiency. Pediatr Res. Oct 2004;56(4):608-14. [Medline].
Tazawa Y, Kobayashi K, Abukawa D, et al. Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients. Mol Genet Metab. Nov 2004;83(3):213-9. [Medline].
Walter JH, Allen JT, Holton JB. Arginosuccinate synthetase deficiency: good outcome despite severe neonatal hyperammonemia. J Inherit Metab Dis. 1992;15(2):282-3. [Medline].

Urea cycle. Compounds that comprise the urea cycle are numbered sequentially, beginning with carbamyl phosphate. At the first step (1), the first waste nitrogen is incorporated into the cycle; also at this step, N-acetylglutamate exerts its regulatory control on the mediating enzyme, carbamyl phosphate synthetase (CPS). Compound 2 is citrulline, the product of condensation between carbamyl phosphate (1) and ornithine (8); the mediating enzyme is ornithine transcarbamylase. Compound 3 is aspartic acid, which is combined with citrulline to form argininosuccinic acid (4); the reaction is mediated by argininosuccinate (ASA) synthetase. Compound 5 is fumaric acid generated in the reaction that converts ASA to arginine (6), which is mediated by ASA lyase.

View Table List

Read more about Citrullinemia on Medscape

About Medscape Reference

[ CLOSE WINDOW ]

About Medscape Reference

Medscape Reference is the most authoritative and accessible point-of-care medical reference for physicians and health care professionals. All content is available free of charge, both online and via mobile devices.

Medscape Reference articles represent the expertise and practical knowledge of top physicians and pharmacists from leading academic medical centers in the US and worldwide. In addition, our rigorous literature survey process allows us to rapidly integrate new practice-changing information into the relevant topics by systematically reviewing the major medical and pharmacy journals, news announcements, and important practice guidelines.

Medscape Reference provides comprehensive coverage across more than 30 medical specialties and is composed of the following areas:

Diseases and Conditions

More than 6,300 evidence-based and physician-reviewed disease and condition articles are organized to rapidly and comprehensively answer clinical questions, as well as to provide in-depth information in support of diagnosis, treatment, and other clinical decision-making. Topics are richly illustrated with more than 30,000 clinical photos and radiographic images.

Procedures

More than 650 clinical procedure articles provide clear, step-by-step instructions, and include instructional videos and images to allow clinicians to master the newest techniques or to improve their skills in procedures they have previously performed.

Drugs

More than 2,100 monographs, including prescription and over-the-counter drugs, plus over 5,000 corresponding brand-name drugs, herbals, and supplements, are provided. Drug images and pricing are also included. In addition, a Drug Interaction Checker provides rapid access to tens of thousands of interactions between brand and generic drugs, over-the-counter drugs, and herbals and supplements.

Anatomy

More than 70 anatomy articles feature clinical images and diagrams of the major human body systems and organs. The articles assist with the understanding of the anatomy involved in treating specific conditions and performing procedures. They can also facilitate physician-patient discussions.

Special Features
Best Evidence

This email newsletter features current and clinically relevant journal citations that are selected via our rigorous literature survey review process. These same citations are incorporated into the relevant Medscape Reference articles. This newsletter serves as a quick and easily accessible way to stay up to date with clinically relevant journal articles that impact clinical practice.

Case Studies

These challenging and classic case presentations provide a quick way for practicing physicians to sharpen their diagnostic and patient-management skills. Each case starts with how the patient presented in the clinic and then using a question and answer format, progresses through diagnosis and on to treatment and includes follow up information about outcome for the patient.

Image collections

Image collections are a visually-engaging presentation of both common and uncommon diseases, case presentations, and current controversies in medicine. They are presented in an image rich, slideshow format and are designed to challenge and expand physicians' knowledge of clinically important topics.

Medscape is the leading online destination for healthcare professionals for clinical information. In addition to clinical reference tools, Medscape also offers:

Medscape News Learn more
Medscape Education Learn more