#229100
ICD+
| |||||||||||||||||||||||||||||||||||||||
| FORMIMINOTRANSFERASE DEFICIENCY | |||||||||||||||||||||||||||||||||||||||
| Alternative titles; symbols | |||||||||||||||||||||||||||||||||||||||
| GLUTAMATE FORMIMINOTRANSFERASE DEFICIENCY FORMIMINOGLUTAMIC ACIDURIA FIGLU-URIA | |||||||||||||||||||||||||||||||||||||||
| Phenotype Gene Relationships | |||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||
| Clinical Synopsis | |||||||||||||||||||||||||||||||||||||||
| TEXT | |||||||||||||||||||||||||||||||||||||||
| A number sign (#) is used with this entry because of evidence that the disorder is caused by mutations in the FTCD gene (606806). | |||||||||||||||||||||||||||||||||||||||
| Description | |||||||||||||||||||||||||||||||||||||||
| Glutamate formiminotransferase deficiency is an autosomal recessive disorder and the second most common inborn error of folate metabolism. Features of a severe phenotype include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematologic abnormalities. | |||||||||||||||||||||||||||||||||||||||
| Clinical Features | |||||||||||||||||||||||||||||||||||||||
| In the 2 related Japanese patients reported by Arakawa et al. (1965, 1966), mental retardation was the main clinical feature. The ferric chloride test was positive due to formiminoglutamic acid in the urine. Other features were marked physical retardation, anemia, megaloblastic bone marrow, and biochemical evidence of disturbed folic acid metabolism. Very large amounts of FIGLU were excreted in the urine. The level of folic acid in the blood was increased. Hyperfolicacidemia followed histidine loading. Arakawa et al. (1965) observed hypersegmentation of the nuclei of neutrophils in 1 case. This may have been fortuitous association of an independent trait, since the father and his sister and mother showed the same finding but were otherwise normal. See Undritz anomaly (191500). Erbe (1977) suggested that mental retardation is not generally a feature of this benign condition, having been included as a result of ascertainment bias in the original studies of Arakawa. Heterogeneity in this category is suggested by the report by Niederwieser et al. (1974) of 2 sisters who had FIGLU in the urine with normal serum folic acid levels. They differed from reported cases of postulated formiminotransferase deficiency in a 10-fold increase in FIGLU excretion with histidine loading, normal hematologic findings, normal serum folic acid, and lack of mental retardation in one. In a further study of the affected Swiss sisters, Niederwieser et al. (1976) postulated 'a practically complete deficiency' of formimino-L-glutamate:tetrahydrofolate-5-formiminotransferase. Their patients did not respond to folic acid. Perry et al. (1975) described similar patients. Rosenblatt (1987) preferred to call this condition glutamate formiminotransferase deficiency. | |||||||||||||||||||||||||||||||||||||||
| See Also: | |||||||||||||||||||||||||||||||||||||||
| Arakawa et al. (1968); Arakawa et al. (1972); Arakawa et al. (1968); Duran et al. (1981); Erbe (1975); Hilton et al. (2003) | |||||||||||||||||||||||||||||||||||||||
| REFERENCES | |||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||