Interpretive Handbook

Test 89899 :
FTCD Gene, Known Mutation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Glutamate formiminotransferase deficiency is an autosomal recessive inborn error of folate and histidine metabolism caused by a deficiency of the enzyme, glutamate formiminotransferase-cyclodeaminase, which is encoded at the FTCD loci on chromosome 21q22.3. Glutamate formiminotransferase deficiency presents as a clinical spectrum that ranges from asymptomatic to severe. Individuals with the severe form of disease are reported to have mental and physical retardation and anemia, whereas the mild form is associated with a lesser degree of developmental delay. Of note, the association of the enzyme deficiency with mental retardation has been disputed in the literature.


An elevated amount of urine formiminoglutamate (FIGLU) is a cardinal sign of glutamate formiminotransferase deficiency for both the severe and mild clinical phenotypes. However, higher levels of urine FIGLU are observed in patients with milder forms of the disease and these levels occur in the absence of histidine loading, whereas the presence of FIGLU in the urine is typically only observed in severe cases after L-histidine administration. In addition, the severe form of disease is associated with elevated serum folate levels, whereas the milder form of disease is not.


As there are discrepancies in FIGLU and serum folate levels among affected individuals, confirmation of suspected cases of glutamate formiminotransferase deficiency may require a liver biopsy for enzymology or the identification of 2 disease-causing mutations in the FTCD gene. Identification of 2 FTCD mutations establishes a molecular diagnosis of glutamate formiminotransferase deficiency, and rules out other diseases associated with high levels of urine FIGLU, such as folate or methylcobalamin deficiencies.


Site-specific testing for mutations that have already been identified in an affected patient is useful for confirming a suspected diagnosis in a family member. It is also useful for determining whether at-risk individuals are carriers of the disease and, subsequently, at risk for having a child with glutamate formiminotransferase deficiency.

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnostic confirmation of glutamate formiminotransferase deficiency when familial mutations have been previously identified


Carrier screening of individuals with a family history of glutamate formiminotransferase deficiency when mutation(s) in the FTCD gene have been identified in a family member


Prenatal testing when 2 familial mutations have previously been identified in an affected family member

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order GFDMS / FTCD Gene, Full Gene Analysis.


Analysis is performed for the known familial mutation(s) only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with mental retardation, high levels of serum folate, or high levels of urine formiminoglutamate.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Hilton JF, Christensen KE, Watkins D, et al: The molecular basis of glutamate formiminotransferase deficiency. Hum Mutat 2003;22:67-73

2. Solans A, Estivill X, de la Luna S: Cloning and characterization of human FTCD on 21q22.3, a candidate gene for glutamate formiminotransferase deficiency. Cytogenet Cell Genet 2000;88:43-49