Glutamate formiminotransferase deficiency
Incidence
Rare. Autosomal recessive. There are 2 types, symptomatic and asymptomatic.
Clinical Characteristics
Affected patients are mentally retarded and/or have convulsions. However, a number of healthy siblings with the biochemical abnormality has been described. Increased urinary forminino glutamic acid in the absence of folic acid deficiency or cobalamine C disease is indicative of formimino transferase deficiency. Accumulation of imidazolone propionic acid is not observed but there is an abnormal excretion of its oxydation product hydantoin-5-priopionic acid. Loading test with histidine will enhance the excretion. Confirmation of the defect is made by enzyme analysis. Probably the liver is the only suitable tissue. Mental retardation can be present from infancy through adolescence. Convulsions can be present in the neonatal period or infancy. Megaloblastic anemia can be present from neonatal period to adolescence. Hypotonia can be present at any age from the neonatal period on. Formimino glutamic acid in urine is elevated at all ages as well as hydantoin-5-priopionic acid in urine. Folic acid levels in blood are normal at all ages. Formimino transferase deficiency is diagnosed by finding glutamic acid (from the decomposition of formimino glutamic acid) and hydantoin-5-priopionic acid in the urine. Probably, this defect does not require treatment. The clinical expression is variable. In type I there is folate responsive megaloblastic anemia, associated in half the cases with mental retardation, hypotonia, abnormal EEG and cortical atrophy. These features start between 2 weeks and 18 months of age. The type II has no symptoms or very mild such as speech defect present. There is no folate deficiency but there is high excretion in urine of formiminoglutamic acid (FIGLU).
Precipitants
no
Provocation Tests
Accumulation of imidazolone propionic acid is not observed but there is an abnormal excretion of its oxydation product hydantoin-5-priopionic acid. Loading test with histidine will enhance the excretion.
Diagnostic Procedures
Formimino transferase deficiency is diagnosed by finding glutamic acid (from the decomposition of formimino glutamic acid) and hydantoin-5-priopionic acid in the urine. There is high excretion in urine of formiminoglutamic acid (FIGLU) which is the hallmark of the condition.