Mackenzie's Mission_Reproductive Carrier Screening

Gene: FTCD

Red List (low evidence)

Literature review

· First reported in the mid 60s – 2 Japanese patients with ID, anemia, megaloblastic bone marrow and biochemical evidence of disturbed folic acid metabolism, specifically large amounts of formiminoglutamate (FIGLU) excreted in the urine. (PMID:5956503,5897668). In the mid 70s, other cases were found with FIGLU-uria but no hematologic abnormalities and mild/no ID (PMID:4413489)
· As early as 1977, it was suggested that ID is not generally a feature of this benign biochemical phenotype, having been included in the original studies as the result of ascertainment bias.
· Most recent paper describing glutamate forminimotransferase deficiency is a newborn screen (Majumdar et al 2017, PMID: 29178637). Of 20 screen-positive patients, 1 had mild development delay and another had DD that was likely due to another etiology. FIGLU was elevated in urine in all tested patients at follow-up but there were no additional developmental concerns/signs of anemia.

Population frequency data

· Population frequency data indicates that numerous FTCD-deficient cases are undiagnosed or unrecognized by either current laboratory testing or from the lack of a clinical presentation.

Expert advice

· The corresponding author on the Majumdar et al 2017 paper writes that “evaluating FTCD for sequence variance would have limited utility for reproductive decisions as the clinical implication of both known and novel FTCD variation is uncertain at best”.

Not suitable for reproductive carrier screening; classify RED - remove from panel

Created: 24 Jul 2021, 12:15 a.m. | Last Modified: 24 Jul 2021, 12:15 a.m.

Panel Version: 0.102

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glutamate formiminotransferase deficiency MIM#229100

Publications

• PMID: 5956503
• 5897668
• 4413489
• 29178637