Bit · Biochem
Vitamin Deficiencies — Water-Soluble vs Fat-Soluble
Thirteen vitamins, thirteen deficiency syndromes. Water-soluble vitamins wash out and rarely store; fat-soluble vitamins do the opposite.
Mechanism
Water-soluble (B-complex, C) are not stored substantially — deficiency develops over weeks. Fat-soluble (A, D, E, K) are stored in liver and adipose — deficiency develops over months, but toxicity is more common.
Differentiator Table
| Vitamin | Function | Deficiency syndrome | Distinctive clue |
|---|---|---|---|
| A (retinol) | Vision pigments, epithelial maintenance | Night blindness, xerophthalmia, Bitot spots, immune dysfunction | Squamous metaplasia |
| D | Ca²⁺ + PO₄³⁻ regulation | Rickets (children), osteomalacia (adults) | Bowed legs, looser zones, low Ca/PO₄ |
| E (tocopherol) | Antioxidant | Hemolytic anemia, ataxia, peripheral neuropathy | Mimics B12 minus megaloblastic |
| K | γ-carboxylation of clotting factors 2,7,9,10,C,S | Bleeding, prolonged PT (then PTT) | Newborn hemorrhagic disease; warfarin reverses K |
| B1 (thiamine) | α-ketoacid dehydrogenases, transketolase | Wet beriberi (high-output HF) / dry beriberi (neuropathy); Wernicke-Korsakoff | Alcoholic with confusion-ataxia-ophthalmoplegia |
| B2 (riboflavin) | FAD/FMN | Cheilosis, corneal vascularization | '2 C's of B2' |
| B3 (niacin) | NAD/NADP | Pellagra — 3 D's: Dermatitis, Diarrhea, Dementia | Casal necklace; tryptophan source |
| B5 (pantothenate) | Coenzyme A | Dermatitis, enteritis, alopecia, adrenal insufficiency | Rare |
| B6 (pyridoxine) | Decarboxylation of AAs, heme synthesis | Sideroblastic anemia, peripheral neuropathy, convulsions | INH → B6 deficiency seizures |
| B7 (biotin) | Carboxylation | Dermatitis, alopecia, enteritis | Raw egg whites (avidin) |
| B9 (folate) | DNA synthesis (methylation) | Megaloblastic anemia WITHOUT neuro signs; neural tube defects | Pregnancy; methotrexate |
| B12 (cobalamin) | Homocysteine→methionine; methylmalonyl-CoA→succinyl | Megaloblastic anemia WITH neuro (subacute combined degeneration); ↑ MMA | Vegans, terminal ileum disease, pernicious anemia |
| C (ascorbate) | Hydroxylation of collagen Pro/Lys; antioxidant | Scurvy — bleeding gums, perifollicular hemorrhages, poor wound healing | Sailors, infants on cow's milk |
The Pivot
Two splits do most of the work:
- Megaloblastic anemia — neuro symptoms? Yes → B12. No → folate.
- Bleeding — PT/PTT prolonged after newborn period? → vitamin K. Bleeding gums, easy bruising in a teenager who only eats white rice → vitamin C.
NBME-Style Stem
A 64-year-old woman presents with progressive numbness, gait instability, and forgetfulness. Hemoglobin is 9.2 g/dL with MCV 116 fL. Hypersegmented neutrophils are seen on peripheral smear. Serum methylmalonic acid and homocysteine are both elevated. Which of the following is the most likely diagnosis?
Concept Anchor
Each vitamin maps to a specific enzyme (or set of enzymes); deficiency manifests as the failure of those enzymes' work. The high-yield trick is the B12/folate split — only B12 deficiency causes neuro deficits and elevated MMA.