Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Ornithine translocase deficiency

Reviewed November 2006

What is ornithine translocase deficiency?

Ornithine translocase 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 translocase deficiency varies widely in its severity and age of onset. An infant with ornithine translocase deficiency may be lacking in energy (lethargic) or refuse to eat, or have poorly controlled breathing or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. Episodes of illness may coincide with the introduction of high-protein formulas or solid foods into the diet.

In most affected individuals, signs and symptoms of ornithine translocase deficiency do not appear until later in life. Later-onset forms of ornithine translocase deficiency are usually less severe than the infantile form. Some people with later-onset ornithine translocase deficiency cannot tolerate high-protein foods, such as meat. Occasionally, high-protein meals or stress caused by illness or periods without food (fasting) may cause ammonia to accumulate more quickly in the blood. This rapid increase of ammonia may lead to episodes of vomiting, lack of energy (lethargy), problems with coordination (ataxia), confusion, or blurred vision. Complications of ornithine translocase deficiency may include developmental delay, learning disabilities, and stiffness caused by abnormal tensing of the muscles (spasticity).

How common is ornithine translocase deficiency?

Ornithine translocase deficiency is a very rare disorder. Fewer than 100 affected individuals have been reported worldwide.

What genes are related to ornithine translocase deficiency?

Mutations in the SLC25A15 gene cause ornithine translocase deficiency.

Ornithine translocase 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. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.

The SLC25A15 gene provides instructions for making a protein called a mitochondrial ornithine transporter. This protein is needed to move a molecule called ornithine within the mitochondria (the energy-producing centers in cells). Specifically, this protein transports ornithine across the inner membrane of mitochondria to the region called the mitochondrial matrix, where it participates in the urea cycle.

Mutations in the SLC25A15 gene result in a mitochondrial ornithine transporter that is unstable or the wrong shape, and which cannot bring ornithine to the mitochondrial matrix. This failure of ornithine transport causes an interruption of the urea cycle and the accumulation of ammonia, resulting in the signs and symptoms of ornithine translocase deficiency.

Related Gene(s)

Changes in this gene are associated with ornithine translocase deficiency.

  • SLC25A15

How do people inherit ornithine translocase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

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

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

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/hyperornithinemia-hyperammonemia-homocitrullinuria-syndrome)
  • Gene Review: Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK97260/)
  • Gene Review: Urea Cycle Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1217/)
  • Genetic Testing Registry: Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268540)
  • 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 translocase deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/ornithine-translocase-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/ornithine-translocase-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 translocase deficiency?

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

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

What other names do people use for ornithine translocase deficiency?

  • HHH syndrome
  • hyperornithinemia-hyperammonemia-homocitrullinemia syndrome
  • hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
  • Triple H syndrome

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 translocase deficiency?

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

What glossary definitions help with understanding ornithine translocase deficiency?

ammonia ; ataxia ; autosomal ; autosomal recessive ; cell ; class ; coma ; compound ; deficiency ; developmental delay ; disabilities ; fasting ; gene ; hyperammonemia ; inherited ; lacking in energy ; lethargic ; lethargy ; mitochondria ; molecule ; nervous system ; newborn screening ; protein ; recessive ; screening ; spasticity ; stress ; syndrome ; toxic ; urea

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

References

  • Camacho JA, Mardach R, Rioseco-Camacho N, Ruiz-Pesini E, Derbeneva O, Andrade D, Zaldivar F, Qu Y, Cederbaum SD. Clinical and functional characterization of a human ORNT1 mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Pediatr Res. 2006 Oct;60(4):423-9. Epub 2006 Aug 28. (http://www.ncbi.nlm.nih.gov/pubmed/16940241?dopt=Abstract)
  • Camacho JA, Obie C, Biery B, Goodman BK, Hu CA, Almashanu S, Steel G, Casey R, Lambert M, Mitchell GA, Valle D. Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter. Nat Genet. 1999 Jun;22(2):151-8. (http://www.ncbi.nlm.nih.gov/pubmed/10369256?dopt=Abstract)
  • Camacho JA, Rioseco-Camacho N, Andrade D, Porter J, Kong J. Cloning and characterization of human ORNT2: a second mitochondrial ornithine transporter that can rescue a defective ORNT1 in patients with the hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a urea cycle disorder. Mol Genet Metab. 2003 Aug;79(4):257-71. (http://www.ncbi.nlm.nih.gov/pubmed/12948741?dopt=Abstract)
  • Korman SH, Kanazawa N, Abu-Libdeh B, Gutman A, Tsujino S. Hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome with evidence of mitochondrial dysfunction due to a novel SLC25A15 (ORNT1) gene mutation in a Palestinian family. J Neurol Sci. 2004 Mar 15;218(1-2):53-8. (http://www.ncbi.nlm.nih.gov/pubmed/14759633?dopt=Abstract)
  • Miyamoto T, Kanazawa N, Hayakawa C, Tsujino S. A novel mutation, P126R, in a Japanese patient with HHH syndrome. Pediatr Neurol. 2002 Jan;26(1):65-7. (http://www.ncbi.nlm.nih.gov/pubmed/11814739?dopt=Abstract)
  • Miyamoto T, Kanazawa N, Kato S, Kawakami M, Inoue Y, Kuhara T, Inoue T, Takeshita K, Tsujino S. Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X. J Hum Genet. 2001;46(5):260-2. (http://www.ncbi.nlm.nih.gov/pubmed/11355015?dopt=Abstract)
  • OMIM: HYPERORNITHINEMIA-HYPERAMMONEMIA-HOMOCITRULLINURIA SYNDROME (http://omim.org/entry/238970)
  • Salvi S, Dionisi-Vici C, Bertini E, Verardo M, Santorelli FM. Seven novel mutations in the ORNT1 gene (SLC25A15) in patients with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Hum Mutat. 2001 Nov;18(5):460. (http://www.ncbi.nlm.nih.gov/pubmed/11668643?dopt=Abstract)
  • Salvi S, Santorelli FM, Bertini E, Boldrini R, Meli C, Donati A, Burlina AB, Rizzo C, Di Capua M, Fariello G, Dionisi-Vici C. Clinical and molecular findings in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. Neurology. 2001 Sep 11;57(5):911-4. (http://www.ncbi.nlm.nih.gov/pubmed/11552031?dopt=Abstract)
  • Torisu H, Kira R, Kanazawa N, Takemoto M, Sanefuji M, Sakai Y, Tsujino S, Hara T. A novel R275X mutation of the SLC25A15 gene in a Japanese patient with the HHH syndrome. Brain Dev. 2006 Jun;28(5):332-5. Epub 2006 Jan 10. (http://www.ncbi.nlm.nih.gov/pubmed/16376511?dopt=Abstract)
  • Tsujino S, Kanazawa N, Ohashi T, Eto Y, Saito T, Kira J, Yamada T. Three novel mutations (G27E, insAAC, R179X) in the ORNT1 gene of Japanese patients with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Ann Neurol. 2000 May;47(5):625-31. (http://www.ncbi.nlm.nih.gov/pubmed/10805333?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.

 
Reviewed: November 2006
Published: July 28, 2014