Folate and Vitamin B12

Deficiency

Ray Angelo C. Robidillo

Advisor: Sir Jolito

Background
Vitamins
Organic compounds that act as metabolic
catalysts
Two groups fat-soluble and water-soluble
Folate and vitamin B12
Water-soluble vitamins important in the
formation of red blood cells, the nervous
system, and DNA
Vit B12(Cobalamin)
Meat and dairy products
Important coenzyme in 2 biochem rxn
isomerization of methylmalonyl coenzyme A
(CoA) to succinyl CoA
transfer of a methyl group from 5-methyl THF
to homocysteine
B12 Metabolism
Folate(B9)
General term used for any form of Vit folic acid
Found in leafy green vegetables, dried beans,
liver and beef
Transfer carbon units in the form of methyl
groups from donors to receptors
B12 and Folate roles in DNA
synthesis
Pathophysiology
Folic acid and vitamin B12
Required for DNA synthesis and red cell maturation

Two vitamins combine in methionine synthase reaction

Methyl group is transferred to homocysteine to make

methionine
Decrease in either leads to increase in homocysteine
level
Megaloblastic Anemia
Deficiency leads to change in RBC shape
Megaloblastic anemia is a subgroup of macrocytic
anemias
Megaloblastic erythropoiesis when defect in DNA synthesis and
the cells are arrested at the G2 phase
Becomes a buildup of cells that do not synthesize DNA so
nucleus develops at a slower rate than the rest of the cell
Cytoplasm continues to grow due to RNA synthesis
Cells become larger and megaloblastic
Causes of Deficiency
B12: Folate:
Ileal disease (TB, Malnutrition: Destroyed by
lymphoma, post- heat during cooking
radiation, Crohns) Alcoholism (decreased in
Fish tapeworm 2-4 days): impairs
(Diphyllobothrium enterohepatic cycle and
latum) infection inhibits absorption
Inadequate Increased requirement in
intake(Vegans) hemolytic anemia,
pregnancy, exfoliative skin
disease
Drugs
Effects on the
Body:Folate

Main manifestations
glossitis, symptoms of anemia (weakness,
pallor, shortness of breath), and GI problems
(weight loss and infertility)

Recommended intake of folate for adults is 400

micrograms per day, and for women of
childbearing age is 600 micrograms per day
Hyperhomocysteinemia
Folate deficiency is number one cause
Hyperhomocysteinemia is less than 12
micromoles per liter
Closely related to CVD
American Heart Association reported that
47% of all patients with CVD had
hyperhomocysteinemia
Effects on the Body:Vit. B12
Main manifestations
same as those for folate but may be a more serious presentation
with peripheral neuropathy, degeneration of the spinal cord, or
demyelination of white matter of brain
Patient may present with difficulty walking, parasthesia, loss of
memory function, and a positive Romberg test
Lab work
also shows an increase in size of MCV
 Subacute Combined
Degeneration
Degeneration and demyelination of the
dorsal (posterior) and lateral spinal
columns
Screening Test
Five tests are used to screen for megaloblastic anemia:
blood count (CBC)Hb values <7-8%

and <20%Hct
reticulocyte count Low retic. count

WBC manual differential count hypersegmented

neutrophils
serum bilirubinInc lvls

lactate dehydrogenaseInc lvls

Specific Diagnostic Tests
Bone Marrow Exam
Reference confirmatory test to identify the
megaloblastic appearance of the developing RBCs.

Folate,B12,MMA and Homocysteine assay

Testing serum or plasma levels using IA
Clinical Findings
Peripheral Blood Bone Marrow
Treatment
Distinguishing between the two vitamin deficiencies
Treatment is to supply the vitamin
Recommended intake of folate for adults is 400 mg/day,
and for pregnant women of its 600 mg/day
Recommended intake of vitamin B12 for adults is 2.4
mg/day, pregnant women its 2.6 mg/day
 Case Study
B12 serum level: 196 | Folate: 7
Symptoms experienced:

Depression Headaches
Paranoia Irritability
Mood swings Mania
Psychosis Tinnitus
Glossitis Premature greying
Chronic fatigue Heavy periods
Weight loss Visual disturbance
Case Study

Sara was vegetarian from her early teens until her early thirties.
Her eyesight was affected at age eighteen and by her thirties
severe depression had set in. Her periods became progressively
more painful and tinnitus and chronic fatigue began.
Sara like many others, had never been screened for physical
reasons for her depression. She was misdiagnosed with bipolar
and was sectioned following a psychotic episode. Her doctor was
completely unaware of the psychiatric manifestations of B12
deficiency and initially refused to even test for either thyroid
dysfunction or B12 deficiency both of which cause psychosis.
Once tested she was shown to be deficient but was refused
treatment as the doctor insisted there were no symptoms present.
 A second doctor would only prescribe low dose oral B12
which was entirely useless for the advanced neurological
symptoms. Eventually after changing doctor a third time,
injection loading doses were given. Luckily Sara is now in
safe hands with a doctor who has updated their previously
poor knowledge of B12 deficiency. She now self injects every
other day and takes a good vitamin B complex and 5mg of
folic acid daily. Her depression and anxiety improve every
day, her periods are far less painful and her tinnitus is
quietening.
Once Sara was given ferrous sulphate to raise her low ferritin
levels her chronic fatigue improved enormously and she is
now firmly on the road to recovery.
 References
Smith LJ, Keohane EM, Walenga JM. Rodaks Hematology:Clinical
Principles and Applications.5th edition. Elsevier Saunders.2012
Wickramsinghe SN. Diagnosis of megaloblastic anemias. Blood Reviews.
2006; 20 (6), 299-318
Porth C. Essentials of Pathophysiology: concepts of altered health status.
Second Edition. Lippincott Williams and Wilkins. 2004; 168-169.
Dale DA, Federman DA, Antman KA, Atkinson JO, Cassel CH, Feldman MA
et al. ACP Medicine. Volume 1. 2006 Edition. New York: WebMD Inc;
2006.
Carmel RA. Laboratory Diagnosis of Megaloblastic Anemia. Medical
Progress. 1978 April;128(4):294-304.
Sener UF, Zorlu YA, Karguzel OG, Ozdamar OZ, Coker IS, et al. Effects of
common anti-epileptic drug monotherapy on serum levels of homocysteine,
Vitamin B12, folic acid and Vitamin B6. Seizure. 2006 Aug 24; 15: 79-85.
Sadeghian SA, Fallahi FA, Salarifar MO, Davoodi GH, Mahmoodian ME,
Fallah NA, et al. Homocysteine, vitamin B12 and folate levels in premature
artery disese. BMC Cardiovascular Disorders. 2006 Sept 26; 6: 38.