This chapter discusses three inborn errors of folate metabolism: congenital folate malabsorption, formiminotransferase deficiency, and dihydrofolate reductase deficiency. They appear to be inherited by an autosomal recessive mechanism.
Eight patients have been described with specific defects in the intestinal absorption of folates. All patients present with folate-responsive severe megaloblastic anemia in early infancy. The majority have mild to severe abnormalities of the CNS. Folic acid absorption tests resulted in flat curves and CSF folate concentration was very low even in the presence of high folate blood levels. Treatment should be early and intensive by parenteral doses of folates to prevent neurologic damage.
The formiminotransferase deficiency syndrome consists of two different types. Type 1 is characterized clinically by severe mental and physical retardation, neurological abnormalities, and muscular hypotonia. Forminoglutamic acid (FIGLU) excretion was increased in response to a histidine load. The treatment of these patients is difficult but it should be tried with pharmacologic doses of folic acid. Type 2 may be a clinically benign disorder. Patients excreted huge amounts of FIGLU. Large doses of folate reduced the FIGLU excretion in some patients.
The three patients reported with dihydrofolate reductase deficiency presented at birth and shortly after birth with congenital megaloblastic anemia. They responded to treatment with 5-formyltetrahydrofolate (5-formyl THF) whereas physiologic doses of folic acid were ineffective. The mutations varied per family.
KeywordsMegaloblastic Anemia Folate Metabolism Cobalamin Deficiency Muscular Hypotonia Serum Folate Level
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