About Urea Cycle Disorders (UCD)
UCDs are inherited metabolic disorders that comprise deficiencies in any of the six enzymes and two transport proteins involved in urea biosynthesis. Inborn errors of urea synthesis lead to an accumulation of ammonia in blood and brain and clinically present as recurrent episodes of hyperammonemia manifested by vomiting, lethargy and coma. UCDs may be diagnosed during neonatal screening, with some milder cases presenting later. Inborn errors of urea synthesis lead to an accumulation of ammonia in blood and brain resulting in poor outcomes, including high rates of mortality and neurodevelopmental disability.
Major Signs and Symptoms
While the onset of severe forms is usually during the neonatal period, less severe forms can occur much later triggered during metabolic stress (e.g. infections, vomiting, surgery etc.) or with more insidious symptoms such as failure to thrive, liver disease, developmental delay, behavioural disorders or psychiatric symptoms.
Incidence and Prevalence
The true incidence of UCD is unknown, with not all cases identified in neonatal screening and some fatal cases going undiagnosed. The incidence of UCDs is estimated to be at least 1 in 35,000 births, with partial defects potentially making the number much higher.
Long-term management is based on minimising the nitrogen load in the urea cycle by minimising dietary protein intake. Thus, patients generally consume a protein-restricted diet in order to minimize the production of ammonia from dietary nitrogen. It is recommended that all UCD patients be monitored for plasma arginine levels and except in arginase 1 deficiency (ARG1D) subtype, most will need L-arginine or L-citrulline supplementation.
Citrulline Easy tablets and Pheburane (sodium phenylbutyrate granules) are available from Orpharma and can be ordered by an approved pharmacist or for Citrulline Easy via our Home Delivery Service.
http://www.ncbi.nlm.nih.gov/books/NBK1217/ (accessed 31 July 2015)
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Krivitzky, L., Babikian, T., et al. (2009). “Intellectual, adaptive, and behavioral functioning in children with urea cycle disorders.” Pediatr Res 66(1): 96-101.
Martin-Hernandez, E., Aldamiz-Echevarria, L., et al. (2014). “Urea cycle disorders in spain: An observational, cross-sectional and multicentric study of 104 cases.” Orphanet Journal of Rare Diseases 9:187: 1-14.
Tuchman, M., Lee, B., et al. (2008). “Cross-sectional multi-center study of patients with urea cycle disorders in the united states.” Mol Genet Metab 94(4): 397-402.