Ornithine transcarbamylase deficiency

Reviewed June 2006

What is ornithine transcarbamylase deficiency?

Ornithine transcarbamylase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

Ornithine transcarbamylase deficiency often becomes evident in the first few days of life. An infant with ornithine transcarbamylase deficiency may be lacking in energy (lethargic) or unwilling to eat, and have poorly-controlled breathing rate or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Complications from ornithine transcarbamylase deficiency may include developmental delay and intellectual disability. Progressive liver damage, skin lesions, and brittle hair may also be seen.

In some affected individuals, signs and symptoms of ornithine transcarbamylase may be less severe, and may not appear until later in life.

How common is ornithine transcarbamylase deficiency?

Ornithine transcarbamylase deficiency is believed to occur in approximately 1 in every 80,000 people.

What genes are related to ornithine transcarbamylase deficiency?

Mutations in the OTC gene cause ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. It processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.

In ornithine transcarbamylase deficiency, the enzyme that starts a specific reaction within the urea cycle is damaged or missing. The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia.

Ammonia is especially damaging to the nervous system, so ornithine transcarbamylase deficiency causes neurological problems as well as eventual damage to the liver.

Related Gene(s)

Changes in this gene are associated with ornithine transcarbamylase deficiency.

How do people inherit ornithine transcarbamylase deficiency?

Ornithine transcarbamylase deficiency is an X-linked disorder. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), mutations in both copies of the gene will cause the disorder. Some females with only one altered copy of the OTC gene also show signs and symptoms of ornithine transcarbamylase deficiency.

Where can I find information about diagnosis or management of ornithine transcarbamylase deficiency?

These resources address the diagnosis or management of ornithine transcarbamylase deficiency and may include treatment providers.

Gene Review: Urea Cycle Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1217/)
Genetic Testing Registry: Ornithine carbamoyltransferase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268542)
MedlinePlus Encyclopedia: Hereditary urea cycle abnormality (http://www.nlm.nih.gov/medlineplus/ency/article/000372.htm)

You might also find information on the diagnosis or management of ornithine transcarbamylase deficiency in Educational resources (http://ghr.nlm.nih.gov/condition/ornithine-transcarbamylase-deficiency/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/ornithine-transcarbamylase-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about ornithine transcarbamylase deficiency?

You may find the following resources about ornithine transcarbamylase deficiency helpful. These materials are written for the general public.

MedlinePlus - Health information
- Encyclopedia: Hereditary urea cycle abnormality (http://www.nlm.nih.gov/medlineplus/ency/article/000372.htm)
- Health Topic: Metabolic Disorders (http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html)
- Health Topic: Newborn Screening (http://www.nlm.nih.gov/medlineplus/newbornscreening.html)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/8391/resources/resources/1)
Educational resources - Information pages
- Madisons Foundation (http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=465)
- Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=664)
Patient support - For patients and families
- Children Living with Inherited Metabolic Diseases (http://www.climb.org.uk/)
- National Organization for Rare Disorders (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/309/viewAbstract)
- National Urea Cycle Disorders Foundation (http://nucdf.org/)
- Urea Cycle Disorders Consortium (http://rarediseasesnetwork.epi.usf.edu/ucdc/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1217/)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Ornithine carbamoyltransferase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268542)
ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22ornithine%20transcarbamylase%20deficiency%22)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Ornithine%20Carbamoyltransferase%20Deficiency%20Disease%5BMAJR%5D)%20AND%20(ornithine%20transcarbamylase%20deficiency%5BTIAB%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/311250)

What other names do people use for ornithine transcarbamylase deficiency?

Ornithine Carbamoyltransferase Deficiency Disease

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about ornithine transcarbamylase deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding ornithine transcarbamylase deficiency?

ammonia ; cell ; chromosome ; class ; coma ; compound ; deficiency ; developmental delay ; enzyme ; gene ; hyperammonemia ; inheritance ; lacking in energy ; lethargic ; nervous system ; neurological ; newborn screening ; protein ; screening ; sex chromosomes ; toxic ; urea

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

Bisanzi S, Morrone A, Donati MA, Pasquini E, Spada M, Strisciuglio P, Parenti G, Parini R, Papadia F, Zammarchi E. Genetic analysis in nine unrelated Italian patients affected by OTC deficiency: detection of novel mutations in the OTC gene. Mol Genet Metab. 2002 Jun;76(2):137-44. (http://www.ncbi.nlm.nih.gov/pubmed/12083811?dopt=Abstract)
Gene Review: Urea Cycle Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1217/)
Gulati S, Menon S, Kabra M, Kalra V. Intermittent hyperammonemic encephalopathy in a child with ornithine transcarbamylase deficiency. Indian J Pediatr. 2004 Jul;71(7):645-7. (http://www.ncbi.nlm.nih.gov/pubmed/15280615?dopt=Abstract)
Huang YT, Chien Y-, Yeh HY, Lin SJ, Lu FL, Chou SP, Lin JM, Chiang SC, Hwu WL. Phenotype and genotype analyses of ornithine transcarbamylase deficiency in Taiwanese. J Formos Med Assoc. 2003 Dec;102(12):851-6. (http://www.ncbi.nlm.nih.gov/pubmed/14976564?dopt=Abstract)
OMIM: ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO (http://omim.org/entry/311250)
Tanaka A, Wada T, Maruyama M, Tanaka A, Takikawa H, Komatsu Y. Hyperammonemia-induced encephalopathy due to ornithine transcarbamylase deficiency in an adult woman: identification of novel missense mutations. J Gastroenterol. 2005 Jan;40(1):106-7. (http://www.ncbi.nlm.nih.gov/pubmed/15692798?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.