Megaloblastic anemia resulting from folic acid
deficiency secondary either to dietary deficiency or malabsorption syndrome.
A genetically transmitted disorder with poor prognosis unless folinic
acid is regularly administered.
Congenital Folate Malabsorption; Hereditary Folate
Malabsorption; Transport Defect Involving Folic Acid.
Not well identified. Twelve cases of this rare
disorder have been reported, mostly in females (but males can be affected).
Folic acid is reduced by dihydrofolate reductase
to form tetrahydrofolate. Tetrahydrofolate is important in one carbon
transfer reaction and essential in the methylation of deoxyuridylate to
thymidylate during DNA synthesis. This leads to megaloblastic anemia,
although the mechanism is poorly understood in nutritional diseases. Folic
acid deficiency is caused by dietary deficiency, impaired absorption, or
increased requirements. Nutritional deficiency is seen in the elderly,
alcoholics, premature infants, infants raised on goat's milk and in
hemodialysis, hyperalimentation, and gastrectomy patients. Impaired
absorption occurs in sprue, regional enteritis, after extensive small bowel
resections, in Whipple disease, and in leukemic infiltration of the
intestine. Increased requirements are seen in pregnancy and in diseases with
increased cell turnover, such as hemolytic anemia.
Clinical signs and symptoms are those of chronic anemia.
Onset is insidious and associated with weakness, palpitation, fatigue,
light-headedness, and dyspnea. Pallor and jaundice are common. Leukocyte and
platelet counts may be depressed. Laboratory features include low serum and
red cell folate, low reticulocyte count, macrocytic anemia, and
hypersegmented neutrophils. Bone marrow examination reveals erythroid
Hereditary form manifests as recurrent
megaloblastic anemia, mental retardation, convulsions, movement disorder
(ataxia), diarrhea, susceptibility to infections, and calcification of basal
ganglia. Most patients die within the first few months of life as a
consequence of diarrhea, vomiting, drowsiness, pallor, and glossitis.
Check hematocrit. Elective surgery
is contraindicated until anemia resolves with treatment. In hereditary
forms, avoid anesthesia unless there is a life-threatening surgical
indication. Most infants are in very poor physical status with malnutrition
and chronic dehydration. Check carefully fluid losses and avoid both
underinflation and overinflation of fluids (intraoperatively and
postoperatively). Provide IV folic acid and consider prophylactic
antibiotics. Check acid balance status and plasma protein levels.
No specific anesthetic consideration
with this condition except for potential severe anemia and epilepsy in the
hereditary form. Transfuse with packed red blood cells as needed.
In hereditary form, reduce doses in
patients with clinical and biologic signs of dehydration.
Dihydropteridine Reductase Deficiency: Same calcification of
basal ganglia and same efficiency of folinic acid therapy.
Phenylketonuria Type II: Inborn error of phenylalanine
metabolism. Results in severe irreversible mental retardation at thrive of
Geller J, Kronn D, Jayabose S, et al: Hereditary folate malabsorption:
Family report and review of the literature. Medicine (Baltimore)
Jebnoun S, Kacem S, Mokrani C, et al: A family study of congenital
malabsorption of folate. J Inherit Metab Dis...