|Values are valid only on day of printing.|
Differential diagnosis and follow-up of patients with urea cycle disorders
Urea cycle disorders (UCD) are a group of inherited disorders of nitrogen detoxification that result when any of the enzymes in the urea cycle (carbamoylphosphate synthetase I: CPS I; ornithine transcarbamylase: OTC; argininosuccinic acid synthetase; argininosuccinic acid lyase; arginase; or the cofactor producer, N-acetyl glutamate synthetase: NAGS), have deficient or reduced activity. The urea cycle serves to break down nitrogen, and defects in any of the steps of the pathway can result in an accumulation of ammonia, which can be toxic to the nervous system. Infants with a complete enzyme deficiency typically appear normal at birth, but present in the neonatal period as ammonia levels rise with lethargy, seizures, hyper- or hypoventilation, and ultimately coma or death. Individuals with partial enzyme deficiency may present later in life, typically following an acute illness or other stressor. Symptoms may be less severe and may present with episodes of psychosis, lethargy, cyclical vomiting, and behavioral abnormalities.
All of the UCDs are inherited as autosomal recessive disorders, with the exception of OTC deficiency, which is X-linked. UCDs may be suspected with elevated ammonia, normal anion gap, and a normal glucose. Plasma amino acids can be used to aid in the diagnosis of a UCD. Measurement of urinary orotic acid, enzyme activity (CPS I, OTC, or NAGS), and molecular genetic testing can help to distinguish the conditions and allows for diagnostic confirmation.
Acute treatment for UCDs consists of dialysis and administration of nitrogen scavenger drugs to reduce ammonia concentration. Chronic management typically involves restriction of dietary protein with essential amino acid supplementation. More recently, orthotopic liver transplantation has been used with success in treating some patients.
< or =23 months: 316-1020 nmol/mL
2-17 years: 329-976 nmol/mL
> or =18 years: 371-957 nmol/mL
< or =23 months: 20-130 nmol/mL
2-17 years: 22-97 nmol/mL
> or =18 years: 38-130 nmol/mL
< or =23 months: 9-38 nmol/mL
2-17 years: 11-45 nmol/mL
> or =18 years: 17-46 nmol/mL
< or =23 months: 29-134 nmol/mL
2-17 years: 31-132 nmol/mL
> or =18 years: 32-120 nmol/mL
Reference value applies to all ages.
The quantitative results of glutamine, ornithine, citrulline, arginine, and argininosuccinic acid with age-dependent reference values are reported without added interpretation. When applicable, reports of abnormal results may contain an interpretation based on available clinical interpretation.
Reference values are for fasting patients.
1. Scriver's The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). Part 8 Amino Acids. Accessed July 6, 2016. Available at: http://ommbid.mhmedical.com/book.aspx?bookid=971
2. Haberle J, Boddaert N, Burlina A, Chakrapani A, et al: Suggested guidelines for diagnosis and management of urea cycle disorders. Orphanet J Rare Dis 2012;7:32
3. Singh RH: Nutritional management of patients with urea cycle disorders. J Inher Metab Dis 2007;30(6):880-887
4. Foshci FG, Morelli MC, Savini S, et al: Urea cycle disorders: A case report of a successful liver transplant and a literature review. World J Gastroenterol 2015 Apr 7;21(13):4063-4068