Test Catalog

Test ID: GFDZ    
FTCD Gene, Full Gene Analysis, Varies

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

Second-tier test for confirming glutamate formiminotransferase deficiency (indicated by biochemical testing or newborn screening)


Ruling out other diseases associated with high levels of urine formiminoglutamate


Carrier screening in cases where there is a family history of glutamate formiminotransferase deficiency but disease-causing mutations have not been identified in an affected individual

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.

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. Evaluation of the FTCD gene by molecular genetic testing is recommended as a second-tier test subsequent to a positive newborn screen or biochemical test.

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.

Interpretation Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

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

A small percentage of individuals who are carriers or have a diagnosis of glutamate formiminotransferase deficiency may have a mutation that is not identified by this method (eg, large genomic deletions, promoter mutations). The absence of a mutation(s), therefore, does not eliminate the possibility of positive carrier status or the diagnosis of glutamate formiminotransferase deficiency. For carrier testing, it is important to first document the presence of a FTCD gene mutation in an affected family member.


In some cases, DNA alterations of undetermined significance may be identified.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


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.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

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

3. 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

Special Instructions Library of PDFs including pertinent information and forms related to the test