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

Glutamate formiminotransferase deficiency

Reviewed August 2009

What is glutamate formiminotransferase deficiency?

Glutamate formiminotransferase deficiency is an inherited disorder that affects physical and mental development. There are two forms of this condition, which are distinguished by the severity of symptoms.

People with the mild form of glutamate formiminotransferase deficiency have minor delays in physical and mental development and may have mild intellectual disability. They also have unusually high levels of a molecule called formiminoglutamate (FIGLU) in their urine.

Individuals affected by the severe form of this disorder have profound intellectual disability and delayed development of motor skills such as sitting, standing, and walking. In addition to FIGLU in their urine, they have elevated amounts of certain B vitamins (called folates) in their blood.

The severe form of glutamate formiminotransferase deficiency is also characterized by megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, and tingling or numbness in the hands and feet.

How common is glutamate formiminotransferase deficiency?

Glutamate formiminotransferase deficiency is a rare disorder; approximately 20 affected individuals have been identified. Of these, about one-quarter have the severe form of the disorder. Everyone reported with the severe form has been of Japanese origin. The remaining individuals, who come from a variety of ethnic backgrounds, are affected by the mild form of the condition.

What genes are related to glutamate formiminotransferase deficiency?

Mutations in the FTCD gene cause glutamate formiminotransferase deficiency. The FTCD gene provides instructions for making the enzyme formiminotransferase cyclodeaminase. This enzyme is involved in the last two steps in the breakdown (metabolism) of the amino acid histidine, a building block of most proteins. It also plays a role in producing one of several forms of the vitamin folate, which has many important functions in the body.

FTCD gene mutations that cause glutamate formiminotransferase deficiency reduce or eliminate the function of the enzyme. It is unclear how these changes are related to the specific health problems associated with the mild and severe forms of glutamate formiminotransferase deficiency, or why individuals are affected by one form or the other.

Related Gene(s)

Changes in this gene are associated with glutamate formiminotransferase deficiency.

  • FTCD

How do people inherit glutamate formiminotransferase 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 glutamate formiminotransferase deficiency?

These resources address the diagnosis or management of glutamate formiminotransferase deficiency and may include treatment providers.

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/formiminoglutamic-acidemia)
  • Genetic Testing Registry: Glutamate formiminotransferase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268609)

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

You may find the following resources about glutamate formiminotransferase 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 glutamate formiminotransferase deficiency?

  • Arakawa syndrome 1
  • FIGLU-uria
  • formiminoglutamic aciduria
  • formiminotransferase deficiency

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 glutamate formiminotransferase deficiency?

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

What glossary definitions help with understanding glutamate formiminotransferase deficiency?

aciduria ; amino acid ; anemia ; autosomal ; autosomal recessive ; breakdown ; cell ; deficiency ; disability ; enzyme ; folate ; gene ; histidine ; inherited ; megaloblastic anemia ; metabolism ; molecule ; motor ; newborn screening ; recessive ; screening ; syndrome ; vitamins

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

References

  • Fowler B. The folate cycle and disease in humans. Kidney Int Suppl. 2001 Feb;78:S221-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11169015?dopt=Abstract)
  • Hilton JF, Christensen KE, Watkins D, Raby BA, Renaud Y, de la Luna S, Estivill X, MacKenzie RE, Hudson TJ, Rosenblatt DS. The molecular basis of glutamate formiminotransferase deficiency. Hum Mutat. 2003 Jul;22(1):67-73. Erratum in: Hum Mutat. 2003 Nov;22(5):416. (http://www.ncbi.nlm.nih.gov/pubmed/12815595?dopt=Abstract)
  • Whitehead VM. Acquired and inherited disorders of cobalamin and folate in children. Br J Haematol. 2006 Jul;134(2):125-36. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16846473?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: August 2009
Published: December 16, 2014