CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 4: F O L IC A C ID D E F IC IE N C Y
47-year-old alcoholic white female has fatigue, malaise, nausea,
vomiting, and poor nutritional intake with macrocytic anemia and no evidence
of pancreatitis, liver disease, or peptic ulcer disease.
Cause of anemia:
Folic acid deficiency.
Molecular basis of macrocytosis:
Abnormal proliferation of erythroid
precursors in the bone marrow, since folate deficiency encumbers the
maturation of these cells by inhibition of deoxyribonucleic acid (DNA)
C L IN IC A L C O R R E L A T IO N
Folate is an essential vitamin, found in green leafy vegetables. It is essential
for many biochemical processes in the body, including DNA synthesis and red
blood cell synthesis. Recently, folate supplementation has been found to be
important in the prevention of fetal neural tube defects such as anencephaly
(absence of brain cerebral cortex and no skull or skin covering the brain), and
spina bifida (spinal cord malformation whereby the meninges are exposed
leading to neurologic deficits). Alcoholics in particular are at risk for folate
deficiency because of impaired gastrointestinal absorption and poor nutrition.
Macrocytic anemia (large red blood cells) may be seen with folate deficiency.
Treatment consists for folic acid replacement (usually 1 mg/day) by mouth
with correction of anemia over the following 1 to 2 months. The diet usually
requires adjustment, and correctable causes addressed (malnutrition in this
case). Notably, folate deficiency in pregnancy has been associated with neural
tube defects (NTDs) in fetuses. It is recommended that mothers take at least
400 |J.g of folic acid 3 months prior to conception to reduce the risk of NTD.
At times, more than 400 |j.g of folic acid per day is recommended prior to con-
ception. Some specific examples include a history of previous NTD, sickle cell
disease, multiple gestations, and Crohn disease.
A PPR O A C H TO FO L A T E A N D D N A SY N T H E SIS
Understand the important metabolic roles of folic acid with production
of thymine, purine synthesis, and methionine.
Be aware of how folate deficiency causes megaloblastic anemia.