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Low plasma citrulline

MedGen UID:
326522
Concept ID:
C1839532
Finding
HPO: HP:0003572

Definition

A decreased concentration of citrulline in the blood. [from HPO]

Conditions with this feature

Ornithine carbamoyltransferase deficiency
MedGen UID:
75692
Concept ID:
C0268542
Disease or Syndrome
Ornithine transcarbamylase (OTC) deficiency can occur as a severe neonatal-onset disease in males (but rarely in females) and as a post-neonatal-onset (also known as "late-onset" or partial deficiency) disease in males and females. Males with severe neonatal-onset OTC deficiency are asymptomatic at birth but become symptomatic from hyperammonemia in the first week of life, most often on day two to three of life, and are usually catastrophically ill by the time they come to medical attention. After successful treatment of neonatal hyperammonemic coma these infants can easily become hyperammonemic again despite appropriate treatment; they typically require liver transplant to improve quality of life. Males and heterozygous females with post-neonatal-onset (partial) OTC deficiency can present from infancy to later childhood, adolescence, or adulthood. No matter how mild the disease, a hyperammonemic crisis can be precipitated by stressors and become a life-threatening event at any age and in any situation in life. For all individuals with OTC deficiency, typical neuropsychological complications include developmental delay, learning disabilities, intellectual disability, attention-deficit/hyperactivity disorder, and executive function deficits.
Hyperammonemia, type III
MedGen UID:
120649
Concept ID:
C0268543
Disease or Syndrome
N-acetylglutamate synthase deficiency is an autosomal recessive disorder of the urea cycle. The clinical and biochemical features of the disorder are indistinguishable from carbamoyl phosphate synthase I deficiency (237300), since the CPS1 enzyme (608307) has an absolute requirement for NAGS (Caldovic et al., 2007).
Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency
MedGen UID:
816734
Concept ID:
C3810404
Disease or Syndrome
Most children with carbonic anhydrase VA (CA-VA) deficiency reported to date have presented between day 2 of life and early childhood (up to age 20 months) with hyperammonemic encephalopathy (i.e., lethargy, feeding intolerance, weight loss, tachypnea, seizures, and coma). Given that fewer than 20 affected individuals have been reported to date, the ranges of initial presentations and long-term prognoses are not completely understood. As of 2021 the oldest known affected individual is an adolescent. Almost all affected individuals reported to date have shown normal psychomotor development and no further episodes of metabolic crisis; however, a few have shown mild learning difficulties or delayed motor skills.
Congenital hyperammonemia, type I
MedGen UID:
907954
Concept ID:
C4082171
Disease or Syndrome
Carbamoyl phosphate synthetase I deficiency is an autosomal recessive inborn error of metabolism of the urea cycle which causes hyperammonemia. There are 2 main forms: a lethal neonatal type and a less severe, delayed-onset type (summary by Klaus et al., 2009). Urea cycle disorders are characterized by the triad of hyperammonemia, encephalopathy, and respiratory alkalosis. Five disorders involving different defects in the biosynthesis of the enzymes of the urea cycle have been described: ornithine transcarbamylase deficiency (311250), carbamyl phosphate synthetase deficiency, argininosuccinate synthetase deficiency, or citrullinemia (215700), argininosuccinate lyase deficiency (207900), and arginase deficiency (207800).
Mitochondrial DNA depletion syndrome 17
MedGen UID:
1684823
Concept ID:
C5231412
Disease or Syndrome
ALDH18A1-related de Barsy syndrome
MedGen UID:
1720006
Concept ID:
C5234852
Disease or Syndrome
De Barsy syndrome, or autosomal recessive cutis laxa type III (ARCL3), is characterized by cutis laxa, a progeria-like appearance, and ophthalmologic abnormalities (summary by Kivuva et al., 2008). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see 219100. Genetic Heterogeneity of de Barsy Syndrome Also see ARCL3B (614438), caused by mutation in the PYCR1 gene (179035) on chromosome 17q25.
Phosphoenolpyruvate carboxykinase deficiency, cytosolic
MedGen UID:
1801754
Concept ID:
C5574905
Disease or Syndrome
Cytosolic phosphoenolpyruvate carboxykinase deficiency causes a defect in gluconeogenesis that results in a 'biochemical signature' of fasting hypoglycemia with high tricarboxylic acid cycle intermediate excretion, particularly of fumarate. Other biochemical anomalies that may be seen during metabolic crisis include ketonuria, dicarboxylic aciduria, and urea cycle dysfunction (Vieira et al., 2017). See PCKDM (261650) for a discussion of mitochondrial PCK (PEPCK2; 614095) deficiency.
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A
MedGen UID:
1841116
Concept ID:
C5830480
Disease or Syndrome
Mitochondrial complex V deficiency nuclear type 4A (MC5DN4A) is an autosomal dominant metabolic disorder characterized by poor feeding and failure to thrive in early infancy. Laboratory studies show increased serum lactate, alanine, and ammonia, suggesting mitochondrial dysfunction. Some affected individuals show spontaneous resolution of these symptoms in early childhood and have subsequent normal growth and development, whereas others show developmental delay with impaired intellectual development and movement abnormalities, including dystonia, ataxia, or spasticity; these neurologic deficits are persistent (Lines et al., 2021, Zech et al., 2022). For a discussion of genetic heterogeneity of mitochondrial complex V deficiency, nuclear types, see MC5DN1 (604273).

Professional guidelines

PubMed

Huang X
Zhejiang Da Xue Xue Bao Yi Xue Ban 2023 Oct 3;52(6):744-750. doi: 10.3724/zdxbyxb-2023-0378. PMID: 37807629Free PMC Article
Peretz RH, Ah Mew N, Vernon HJ, Ganetzky RD
Mol Genet Metab 2021 Sep-Oct;134(1-2):37-42. Epub 2021 Jun 24 doi: 10.1016/j.ymgme.2021.06.007. PMID: 34176718Free PMC Article
Molema F, Gleich F, Burgard P, van der Ploeg AT, Summar ML, Chapman KA, Barić I, Lund AM, Kölker S, Williams M; Additional individual contributors from E-IMD
J Inherit Metab Dis 2019 Nov;42(6):1162-1175. Epub 2019 Feb 27 doi: 10.1002/jimd.12066. PMID: 30734935

Curated

American College of Medical Genetics and Genomics, Algorithm, Decreased Citrulline, 2022

Recent clinical studies

Etiology

Piton G, Belin N, Barrot L, Belon F, Cypriani B, Navellou JC, Capellier G
Shock 2015 Nov;44(5):438-44. doi: 10.1097/SHK.0000000000000440. PMID: 26196845
Ware LB, Magarik JA, Wickersham N, Cunningham G, Rice TW, Christman BW, Wheeler AP, Bernard GR, Summar ML
Crit Care 2013 Jan 17;17(1):R10. doi: 10.1186/cc11934. PMID: 23327349Free PMC Article
Noordally SO, Sohawon S, Semlali H, Michely D, Devriendt J, Gottignies P
Nutr Clin Pract 2012 Aug;27(4):527-32. Epub 2012 Jun 15 doi: 10.1177/0884533612449360. PMID: 22706681
Piton G, Manzon C, Monnet E, Cypriani B, Barbot O, Navellou JC, Carbonnel F, Capellier G
Intensive Care Med 2010 Apr;36(4):702-6. doi: 10.1007/s00134-010-1751-6. PMID: 20084502
Chiong MA, Carpenter K, Christodoulou J
J Inherit Metab Dis 2007 Jun;30(3):405. Epub 2007 Apr 3 doi: 10.1007/s10545-007-0495-0. PMID: 17407001

Diagnosis

Wongkittichote P, Ganetzky RD, Demczko MM, Hong X, He M, Master SR
Clin Chem 2023 Jun 1;69(6):661-664. doi: 10.1093/clinchem/hvad039. PMID: 37258485
Piton G, Belin N, Barrot L, Belon F, Cypriani B, Navellou JC, Capellier G
Shock 2015 Nov;44(5):438-44. doi: 10.1097/SHK.0000000000000440. PMID: 26196845
Ware LB, Magarik JA, Wickersham N, Cunningham G, Rice TW, Christman BW, Wheeler AP, Bernard GR, Summar ML
Crit Care 2013 Jan 17;17(1):R10. doi: 10.1186/cc11934. PMID: 23327349Free PMC Article
Piton G, Manzon C, Monnet E, Cypriani B, Barbot O, Navellou JC, Carbonnel F, Capellier G
Intensive Care Med 2010 Apr;36(4):702-6. doi: 10.1007/s00134-010-1751-6. PMID: 20084502
Chiong MA, Carpenter K, Christodoulou J
J Inherit Metab Dis 2007 Jun;30(3):405. Epub 2007 Apr 3 doi: 10.1007/s10545-007-0495-0. PMID: 17407001

Therapy

Yamamoto S, Yamashita S, Kakiuchi T, Kurogi K, Nishi TM, Tago M, Yamashita SI
Am J Case Rep 2022 Nov 15;23:e937658. doi: 10.12659/AJCR.937658. PMID: 36377209Free PMC Article
Ware LB, Magarik JA, Wickersham N, Cunningham G, Rice TW, Christman BW, Wheeler AP, Bernard GR, Summar ML
Crit Care 2013 Jan 17;17(1):R10. doi: 10.1186/cc11934. PMID: 23327349Free PMC Article
Felig DM, Brusilow SW, Boyer JL
Gastroenterology 1995 Jul;109(1):282-4. doi: 10.1016/0016-5085(95)90295-3. PMID: 7797025

Prognosis

Piton G, Belin N, Barrot L, Belon F, Cypriani B, Navellou JC, Capellier G
Shock 2015 Nov;44(5):438-44. doi: 10.1097/SHK.0000000000000440. PMID: 26196845
Piton G, Manzon C, Cypriani B, Carbonnel F, Capellier G
Intensive Care Med 2011 Jun;37(6):911-7. Epub 2011 Mar 12 doi: 10.1007/s00134-011-2172-x. PMID: 21400011
Piton G, Manzon C, Monnet E, Cypriani B, Barbot O, Navellou JC, Carbonnel F, Capellier G
Intensive Care Med 2010 Apr;36(4):702-6. doi: 10.1007/s00134-010-1751-6. PMID: 20084502

Clinical prediction guides

Piton G, Belin N, Barrot L, Belon F, Cypriani B, Navellou JC, Capellier G
Shock 2015 Nov;44(5):438-44. doi: 10.1097/SHK.0000000000000440. PMID: 26196845
Noordally SO, Sohawon S, Semlali H, Michely D, Devriendt J, Gottignies P
Nutr Clin Pract 2012 Aug;27(4):527-32. Epub 2012 Jun 15 doi: 10.1177/0884533612449360. PMID: 22706681
Piton G, Manzon C, Monnet E, Cypriani B, Barbot O, Navellou JC, Carbonnel F, Capellier G
Intensive Care Med 2010 Apr;36(4):702-6. doi: 10.1007/s00134-010-1751-6. PMID: 20084502

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, Decreased Citrulline, 2022

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