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Description
Glutamate formiminotransferase deficiency is a rare inherited disorder that can affect development.
In the past, researchers recognized a mild form and a severe form of glutamate formiminotransferase deficiency. Researchers have since found people who received a diagnosis of glutamate formiminotransferase deficiency as infants who do not appear to have any related health problems. Researchers are actively working to learn more about this condition.
The signs and symptoms associated with glutamate formiminotransferase deficiency have ranged from mild developmental delays with high urine levels of a molecule called formiminoglutamate (FIGLU) to more severe intellectual disabilities and 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).
Frequency
Glutamate formiminotransferase deficiency has an estimated incidence of between 1 in 46,000 people and 1 in 60,000 people, but fewer than 100 people with this condition have been reported in the medical literature. Individuals with the severe form of the disorder have all been of Japanese ancestry.
Causes
Variants (also called mutations) in the FTCD gene cause glutamate formiminotransferase deficiency. The FTCD gene provides instructions for making an enzyme that is involved in the breakdown of histidine, which is a building block (amino acid) of many different proteins. One of the enzyme's jobs is to convert FIGLU to a molecule called 5-formiminotetrahydrofolate.
The FTCD gene variants that cause glutamate formiminotransferase deficiency alter the function of the FTCD enzyme, which disrupts the enzyme’s ability to completely break down histidine. This can cause FIGLU to build up in the body and be released in the urine. It is unclear exactly how these changes are related to the specific health problems seen in some people with glutamate formiminotransferase deficiency.
Inheritance
This condition is inherited in an autosomal recessive pattern
, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Arakawa syndrome 1
- FIGLU-uria
- Formiminoglutamic acidemia
- Formiminoglutamic aciduria
- Formiminotransferase cyclodeaminase deficiency
- Formiminotransferase deficiency
- FTCD deficiency
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Ahrens-Nicklas RC, Ganetzky RD, Rush PW, Conway RL, Ficicioglu C. Characteristics and outcomes of patients with formiminoglutamic aciduria detected through newborn screening. J Inherit Metab Dis. 2019 Jan;42(1):140-146. doi: 10.1002/jimd.12035. Citation on PubMed
- Fowler B. The folate cycle and disease in humans. Kidney Int Suppl. 2001 Feb;78:S221-9. doi: 10.1046/j.1523-1755.2001.59780221.x. Citation on PubMed
- 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. doi: 10.1002/humu.10236. Citation on PubMed
- Majumdar R, Yori A, Rush PW, Raymond K, Gavrilov D, Tortorelli S, Matern D, Rinaldo P, Feldman GL, Oglesbee D. Allelic spectrum of formiminotransferase-cyclodeaminase gene variants in individuals with formiminoglutamic aciduria. Mol Genet Genomic Med. 2017 Nov;5(6):795-799. doi: 10.1002/mgg3.333. Epub 2017 Sep 11. Citation on PubMed
- Niederwieser A, Giliberti P, Matasovic A, Pluznik S, Steinmann B, Baerlocher K. Folic acid non-dependent formiminoglutamic aciduria in two siblings. Clin Chim Acta. 1974 Aug 20;54(3):293-316. doi: 10.1016/0009-8981(74)90248-4. No abstract available. Citation on PubMed
- Whitehead VM. Acquired and inherited disorders of cobalamin and folate in children. Br J Haematol. 2006 Jul;134(2):125-36. doi: 10.1111/j.1365-2141.2006.06133.x. Citation on PubMed
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