For Quick Alerts
ALLOW NOTIFICATIONS  
For Daily Alerts

Urea Cycle Disorders - Causes, Symptoms, Diagnosis And Treatment

Urea cycle disorders (UCDs) are a rare group of diseases, which cause difficulty in removing waste from the body after digestion. UCDs affect the removal of waste that is made from breaking down protein. Protein is essential for the proper functioning of your body, which can be obtained through the consumption of dairy products, meat, fish etc. The consumed protein is then required to be broken down into amino acids, so as to be utilised by your body [1] .

UCDs are inherited diseases and occurs in both children and adults. It can be passed down from the parent to the child. The disorders are included in the category of inborn errors of metabolism. That is, the disorders develop as a result of genetic mutations that cause defects in the nitrogen (extra) metabolism [2] [3] .

UCDs are extremely rare. It happens to one in 30,000 newborns. The onset of the disorders can be neonatal onset or late onset. About 69% of the disorder develop after the newborn period (neonatal onset) [4] .

In the case of newborns, the disorder will result in them being fatally ill within the first 36-48 hours of birth. Whereas for adults, the disorder can go unnoticed for a long period of time. Because, in comparison to infants, adults tend to develop it in mild form and can still produce urea cycle enzymes that will aid in removing the ammonia. This will go on until an internal complication interferes with the function of the enzyme [5] .

Types Of Urea Cycle Disorders

The UCDs are of eight different types. The disorders are named in accordance with the missing component in the urea cycle [6] [7] .

  • ARG1 deficiency - Arginase
  • ASL deficiency - Argininosuccinate lyase
  • ASS1 deficiency - Argininosuccinate synthase 1
  • Citrin deficiency - Citrin
  • CPSI deficiency - Carbamoyl phosphate synthetase I
  • NAGS deficiency - N-acetylglutamate synthase
  • ORNT1 deficiency - Ornithine translocase
  • OTC deficiency - Ornithine transcarbamylase

Causes Of Urea Cycle Disorders

The genetic disorders are passed down from the parent to the child. In order for an infant to develop the condition, they must receive a defective gene from both the parents. However, there is an exception in the case of OTC, as it is passed down from the mother to the child (mostly male).

If both the parents have the defective gene, there is [8] [9]

  • a 25 per cent chance that the child will develop the disorder.
  • a 50 per cent chance that the child will receive one defective gene from one of the parents. That is, the child will not show symptoms of the disorder as the child is a carrier.
  • a 25 per cent chance the child will receive both working genes, one from each parent, and will be unaffected.

In the case of OTC deficiency, the development of the disorder is dependent on the fact that whether the child is male or female. If the mother is the carrier of the defective gene, there is [10] [11]

  • a 50 per cent chance that the male child will receive the normal gene and be unaffected.
  • a 50 per cent chance that the male child will receive the defective gene from the mother, and will be affected.
  • a 50 per cent chance that the female child will receive the abnormal gene, and will be at the risk of having symptoms related to OTC deficiency.
  • a 50 per cent chance that the female child will not receive the abnormal gene, and will be unaffected.

Symptoms Of Urea Cycle Disorders

The signs of the disorder vary according to the age of onset and the type of the disorder. In accordance with the symptoms, UCDs fall into two categories: complete UCD and partial UCD.

When the infant or the adult has partial UCD (the affected will be able to make some of the enzymes), the symptoms will be [12]

  • behaviour problems, including hyperactivity,
  • loss of appetite,
  • mental problems such as confusion, delusions, hallucinations, psychosis,
  • avoiding foods high in protein or a dislike of meat, and
  • nausea or vomiting.

The symptoms of partial UCD may not be noticed for months, or in some cases even years.

In the case of complete UCD, which is the complete lack of an enzyme, the symptoms will be noticeable. It usually develops in infants and will arise within the first couple of days. The symptoms will be [13] [14]

  • fast breathing that becomes slow,
  • problems with posture,
  • fussy,
  • low body temperature,
  • sleepy or sluggish,
  • coma,
  • can't feed,
  • vomiting, and
  • seizures.

Diagnosis Of Urea Cycle Disorders

The doctor will examine the development of UCDs by carrying out urine tests and blood tests. These tests will aid the doctor in analysing the high ammonia levels and the abnormal metabolites (a substance that is produced by metabolism)[15] .

The doctor will carry out a liver biopsy so as to analyse the levels of enzyme activity.

Genetic tests will be carried out to understand the possibility of problems with the genes that are required to break down the proteins in the urea cycle. This will help in identifying and understanding the exact type of UCD [16] [17] .

An MRI or a CT scan will be carried out to examine whether there are any swellings in the brain; caused by the presence of ammonia in the blood.

Treatment For Urea Cycle Disorders

The disorder requires lifelong treatment, which will not essentially cure the condition. However, it will help in managing the symptoms [18] [19] [20] .

1. Medications

In some cases, medications will be required to remove the extra nitrogen and ammonia from the body.

2. Low protein, high-calorie diet

The individual will be required to undergo diets that avoid protein-rich foods. They can consume calorie-rich foods such as fruits, vegetables and starches. With time, the dietician will help in incorporating protein into your daily diet, as it is inevitable for growth.

3. Amino acid supplements

These will be required depending upon the type of the UCD the individual has. Amino acid supplements such as arginine or citrulline may be added to the diet, so as to aid your body in developing proteins required for tissue repair and growth.

4. Liver transplantation

As the production of urea cycle enzymes is carried out in the liver, a liver transplant will help in treating the disorder.

Some of the other ways are by drinking plenty of water, consuming supplements of fat and sugar and dialysis to remove ammonia from the blood.

View Article References
  1. [1] Enns, G. M., Berry, S. A., Berry, G. T., Rhead, W. J., Brusilow, S. W., & Hamosh, A. (2007). Survival after treatment with phenylacetate and benzoate for urea-cycle disorders. New England Journal of Medicine, 356(22), 2282-2292.
  2. [2] Häberle, J., Boddaert, N., Burlina, A., Chakrapani, A., Dixon, M., Huemer, M., ... & Servais, A. (2012). Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet journal of rare diseases, 7(1), 32.
  3. [3] Summar, M. (2001). Current strategies for the management of neonatal urea cycle disorders. The Journal of pediatrics, 138(1), S30-S39.
  4. [4] Leonard, J. V., & Morris, A. A. M. (2002, February). Urea cycle disorders. In Seminars in neonatology (Vol. 7, No. 1, pp. 27-35). WB Saunders.
  5. [5] Summar, M. L., Koelker, S., Freedenberg, D., Le Mons, C., Haberle, J., Lee, H. S., ... & Members of the Urea Cycle Disorders Consortium. (2013). The incidence of urea cycle disorders. Molecular genetics and metabolism, 110(1-2), 179-180.
  6. [6] Mew, N. A., Simpson, K. L., Gropman, A. L., Lanpher, B. C., Chapman, K. A., & Summar, M. L. (2017). Urea cycle disorders overview. In GeneReviews®[Internet]. University of Washington, Seattle.
  7. [7] Uchino, T., Endo, F., & Matsuda, I. (1998). Neurodevelopmental outcome of long‐term therapy of urea cycle disorders in Japan. Journal of inherited metabolic disease, 21, 151-159.
  8. [8] Summar, M. L., Dobbelaere, D., Brusilow, S., & Lee, B. (2008). Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21‐year, multicentre study of acute hyperammonaemic episodes. Acta paediatrica, 97(10), 1420-1425.
  9. [9] Deignan, J. L., Cederbaum, S. D., & Grody, W. W. (2008). Contrasting features of urea cycle disorders in human patients and knockout mouse models. Molecular genetics and metabolism, 93(1), 7-14.
  10. [10] Foschi, F. G., Morelli, M. C., Savini, S., Dall’Aglio, A. C., Lanzi, A., Cescon, M., ... & Stefanini, G. F. (2015). Urea cycle disorders: a case report of a successful treatment with liver transplant and a literature review. World Journal of Gastroenterology: WJG, 21(13), 4063.
  11. [11] Husson, M. C., Schiff, M., Fouilhoux, A., Cano, A., Dobbelaere, D., Brassier, A., ... & Guffon, N. (2016). Efficacy and safety of iv sodium benzoate in urea cycle disorders: a multicentre retrospective study. Orphanet journal of rare diseases, 11(1), 127.
  12. [12] Huh, L., & Farrell, K. (2011). Urea cycle disorders. The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children, 246.
  13. [13] assogne, M. C., Heron, B., Touati, G., Rabier, D., & Saudubray, J. M. (2005). Urea cycle defects: management and outcome. Journal of inherited metabolic disease, 28(3), 407-414.
  14. [14] Leonard, J. V., & Morris, A. A. M. (2002, February). Urea cycle disorders. In Seminars in neonatology (Vol. 7, No. 1, pp. 27-35). WB Saunders.
  15. [15] Häberle, J., Boddaert, N., Burlina, A., Chakrapani, A., Dixon, M., Huemer, M., ... & Servais, A. (2012). Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet journal of rare diseases, 7(1), 32.
  16. [16] Smith, W., Kishnani, P. S., Lee, B., Singh, R. H., Rhead, W. J., King, L. S., ... & Summar, M. (2005). Urea cycle disorders: clinical presentation outside the newborn period. Critical care clinics, 21(4), S9-S17.
  17. [17] Bachmann, C., & Colombo, J. P. (1980). Diagnostic value of orotic acid excretion in heritable disorders of the urea cycle and in hyperammonemia due to organic acidurias. European journal of pediatrics, 134(2), 109-113.
  18. [18] Enns, G. M., Berry, S. A., Berry, G. T., Rhead, W. J., Brusilow, S. W., & Hamosh, A. (2007). Survival after treatment with phenylacetate and benzoate for urea-cycle disorders. New England Journal of Medicine, 356(22), 2282-2292.
  19. [19] Maestri, N. E., Hauser, E. R., Bartholomew, D., & Brusilow, S. W. (1991). Prospective treatment of urea cycle disorders. The Journal of pediatrics, 119(6), 923-928.
  20. [20] Whitington, P. F., Alonso, E. M., Boyle, J. T., Molleston, J. P., Rosenthal, P., Emond, J. C., & Millis, J. M. (1998). Liver transplantation for the treatment of urea cycle disorders. Journal of inherited metabolic disease, 21, 112-118.

Story first published: Thursday, February 28, 2019, 12:47 [IST]
We use cookies to ensure that we give you the best experience on our website. This includes cookies from third party social media websites and ad networks. Such third party cookies may track your use on Boldsky sites for better rendering. Our partners use cookies to ensure we show you advertising that is relevant to you. If you continue without changing your settings, we'll assume that you are happy to receive all cookies on Boldsky website. However, you can change your cookie settings at any time. Learn more