Q- A 45-year-old female presents to her primary care doctor with fatigue and tingling/numbness in her extremities (bilateral). Examination reveals a beefy red and fissured tongue. Further evaluation reveals a low Glutathione reductase activity in the red blood cells. Which of the following vitamin deficiencies could have caused her symptoms?
C. Vitamin B2
E. Vitamin B12
The correct option is C- vitamin B2.
The patient is most probably suffering from Vitamin B2 deficiency (Riboflavin deficiency). Most prominent effects of vitamin B2 deficiency are seen on the skin, mucosa and eyes. The characteristic symptoms are: Glossitis (magenta tongue, geographical tongue), cheilosis, angular stomatitis (fissures at the corners of the mouth), sore throat, burning of the lips, mouth, and tongue, inflammed mucous membranes, seborrheic dermatitis (moist scaly skin inflammation), and corneal vascularization associated with sensitivity to bright light and impaired vision.
Riboflavin deficiency rarely occurs in isolation, mostly it is found in association with deficiencies of other B-complex vitamins. It is frequent in chronic alcoholics. It can also occur in patients with chronic liver diseases, and in hospitalized patients who receive total parenteral nutrition (TPN) with inadequate riboflavin supplementation.
Riboflavin is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin supports energy production by aiding in the metabolism of fats, carbohydrates, and proteins.
In the body, riboflavin occurs primarily as an integral component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).These coenzymes participate in a large majority of the reactions in the body.
Enzymes that contain flavin adenine dinucleotide (FAD) or flavin-mononucleotide (FMN) as prosthetic groups are known as flavoenzymes.
- Flavoproteins play very important roles in the electron transport chain
- Decarboxylation of pyruvate and α-Keto glutarate requires FAD besides other coenzymes.
- FAD is required as a coenzyme for, monoamine oxidase and glutathione reductase.
- Fatty acyl CoA dehydrogenase requires FAD in fatty acid oxidation
- Oxidative Deamination of amino acids require flavoproteins
- FAD is required for the conversion of Succinate to fumarate.
- Mitochondrial Glycerol-3- p dehydrogenase requires FAD
- FAD is required in the conversion of Xanthine to uric acid.
- FAD is required by Glycine oxidase enzyme.
- FAD is a cofactor for methyl tetrahydrofolate reductase and therefore modulates homocysteine metabolism.
The vitamin also plays a role in drug and steroid metabolism, including detoxification reactions
Body status of Riboflavin can be determined by direct and indirect methods.
1) Direct methods include the determination of FAD and FMN in whole blood by HPLC (High Performance Liquid Chromatography). Another way for riboflavin status assessment is the monitoring of urinary excretion.
2) Indirect methods include determining the activity of the FAD dependent erythrocyte glutathione reductase (EGR). This biochemical method gives a valid indication of riboflavin status.
Glutathione reductase is an FAD-dependent enzyme that participates in the redox cycle of glutathione. Reduced glutathione acts as a scavenger for dangerous oxidative metabolites in the cell. With the help of the enzyme glutathione peroxidase, reduced glutathione converts harmful hydrogen peroxide to water. Glutathione reductase (GR) requires FAD to regenerate two molecules of reduced glutathione from oxidized glutathione (figure).
Figure- HMP (hexose mono phosphate pathway) is the major source of NADPH which is required for the conversion of Oxidized to reduced glutathione. Reduced glutathione is required for the activity of glutathione peroxidase, an antioxidant Selenium containing metalloenzyme enzyme that decomposes hydrogen peroxide to water.
The erythrocyte glutathione reductase activation coefficient (EGRac) assay assesses riboflavin status by measuring the activity of GR before and after in vitro reactivation of its prosthetic group FAD; EGRac is calculated as the ratio of FAD-stimulated to unstimulated enzyme activity and indicates the degree of tissue saturation with riboflavin.
As regards other options
A. Vitamin C – deficiency is manifested as Scurvy (bleeding gums, loose teeth and brittle bones).
B. Niacin – Deficiency is manifested as Pellagra (4Ds- Diarrhea, dementia, dermatitis and death)
D. B6-P – No specific deficiency disorder, but the symptoms are mainly neurological, dermatological and hematological (Sideroblastic anemia).
E.Vitamin B12- Megaloblastic anemia, beefy tongue and neurological symptoms are observed in B12 deficiency which coexists with folic acid deficiency.
The most appropriate option therefore is C- B2 deficiency which is determined by measuring the activity of Glutathione reductase.
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