Formiminotransferase deficiency

Malvagia S, la Marca G, Casetta B, et al (2006) Falsely elevated C4-carnitine as expression of glutamate formiminotransferase deficiency in tandem mass spectrometry newborn screening. J Mass Spectrom 41 263-265... 

CFD is further associated with the following inherited metabolic disorders 5,10-methylen-tetrahydrofolate reductase (MTHFR) deficiency [7], 3-phos-phoglycerate dehydrogenase (PGDH) deficiency [8], dihydropteridine reductase (DHPR) deficiency [9], as well as with Rett syndrome [10], and Aicardi-Gou res Syndrome [11]. Furthermore, folate deficiency may be associated with congenital folate malabsorption, severe malnutrition, and formiminotransferase deficiency. 

F-13) Formiminotransferase deficiency. This results in increased urinary levels of FIGlu (for-miminoglutamate). The patient may have significant neurological and other physical defects. FIGlu is also an indicator for folate deficiency. Just as xanthurenate is for Be deficiency (see 57), and urinary methylmalonate is for Bi2 deficiency (see 72). 

A total of 10 patients have now been described with formiminotransferase deficiency. Some have had a variable degree of mental retardation and a severe anemia while others have been asymptomatic. Arakana and his colleagues described five patients (two of whom were brothers) and all were severely mentally retarded (A9, AlO). 

It is not possible to say if all of these patients are true examples of formiminotransferase deficiency. A degree of clinical variation could be expected and this would depend on how much of the active enzyme was available. The patients described by Perry excreted much more formimino-... 

A8. Arakawa, T., Tamura, T., Higashi, O., Ohara, K., Tanno, K., Honda, Y., Narisawa, K., Konno, T., Wada, Y., Sato, Y., and Mizuno, T., Formiminotransferase deficiency syndrome associated with megaloblastic anaemia responsive to pyridoxine or folic acid. Tohoku J. Exp. Med. 94, 3-16 (1968). 

Increased urinary formiminoglutamic acid in the absence of folic acid deficiency or cobalamine C disease is indicative of formiminotransferase deficiency. Accumulation of imidazolonepropionic acid is not observed, but there is an abnormal excretion of its oxidation product, hydantoin-5-pro-pionic acid. Loading tests with histidine will enhance the excretion. Confirmation of the defect is made by enzyme analysis probably the liver is the only suitable tissue. Affected patients were mentally retarded and/or had convulsions however, a number of healthy siblings with the biochemical abnormality have been described. 

The responses of histidine and its metabolites in blood and urine to histidine and urocanic acid loads in patients with histidinemia, urocanase deficiency and formiminotransferase deficiency. 

Although cDNAs encoding human histidase and formiminotransferase have already been cloned, mutation analysis is not performed in patients with histidinemia and formiminotransferase deficiency. cDNA for human urocanase is not cloned. 

Similarly, a deficiency of glutamate formiminotransferase leads to accumulation of Figlu and high levels of serum folate. 

Formimino- transferase deficiency Formiminotransferase Liver 21q223 229100... 

Arakawa, T., Ohara, K., Kudo, Z., Tada, K., Hayashi, T. and Mizuno, T. (1963), Hyperfolic-acidemia with formiminoglutamic-aciduria following histidine loading Suggested for a case of congenital deficiency in formiminotransferase. TohokuJ. Exp. Med., 80,370. 

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