A 34-year-old man presents with dysphagia. The patient says that he has pain on swallowing which gradually onset 2 weeks ago and has not improved. He denies any change in diet but does say that he recently returned from a prolonged work trip to the Caribbean. No significant past medical history or current medications. On physical examination, the patient looks pale. His tongue is swollen and has a beefy, red appearance. Angular stomatitis is present. Laboratory findings are significant for macrocytic, megaloblastic anemia, decreased serum folate, increased serum homocysteine, and normal methylmalonic acid levels. Which of the following conditions most likely caused this patient’s symptoms?

Diphyllobothrium latum infection

Autoimmune destruction of parietal cells

A 17-year-old high school student presents to your office for recent mood and skin changes. The patient is a high school senior who is competing on the wrestling team and recently has lost weight to drop two weight classes over the past several months. He states he has dry, cracking, and irritated skin, as well as a sensation of tingling in his hands and feet. The patient also states that he has not been feeling himself lately. He finds himself more irritable and no longer enjoys many of the activities he once enjoyed. He finds that he often feels fatigued and has trouble concentrating. The patient does not have a significant past medical history and is not on any current medications. The patient admits to drinking alcohol and smoking marijuana on special occasions. He states that he uses supplements that his other team members use. Physical exam is significant for acne, dry, cracked skin around the patient's mouth in particular, and decreased sensation in his lower extremities. Laboratory values are as follows: Serum: Na+: 137 mEq/L Cl-: 101 mEq/L K+: 4.1 mEq/L HCO3-: 24 mEq/L BUN: 15 mg/dL Glucose: 79 mg/dL Creatinine: 0.9 mg/dL Ca2+: 9.2 mg/dL Mg2+: 1.5 mEq/L Homocysteine: 11.2 µmol/L (normal: 4.6 to 8.1 µmol/L) AST: 11 U/L ALT: 11 U/L Alkaline phosphatase: 27 U/L Albumin: 4.5 g/dL Total protein: 6.9 g/dL Total bilirubin: 0.5 mg/dL Direct bilirubin: 0.3 mg/dL Which of the following is the most likely diagnosis?

Water soluble vitamin deficiency

Depression secondary to dietary changes

Water-soluble vitamins - B complex — USMLE Lesson

B1, B2, B3 - Metabolic Powerhouses

Pellagrous dermatitis on legs and arms

Vitamin	Active Form(s)	Key Function (Coenzyme for)	Deficiency Syndromes	Classic Presentation
B1 (Thiamine)	Thiamine Pyrophosphate (TPP)	Dehydrogenase reactions (Pyruvate, α-KG, Transketolase)	Wernicke-Korsakoff Syndrome, Beriberi (Wet/Dry)	Wernicke triad: Confusion, Ophthalmoplegia, Ataxia. Korsakoff: Confabulation, amnesia.
B2 (Riboflavin)	FAD, FMN	Redox reactions (e.g., Succinate Dehydrogenase)	Ariboflavinosis	The 2 C's: Cheilosis (lip inflammation, fissures), Corneal vascularization. Magenta tongue.
B3 (Niacin)	NAD+, NADP+	Redox reactions (Dehydrogenases)	Pellagra	📌 The 3 D's: Diarrhea, Dementia, Dermatitis (C3/C4 dermatome "broad collar" rash).

B9 & B12 - The Anemia Duo

Shared Function: Essential for DNA synthesis (purine & thymidine). Deficiency in either leads to megaloblastic anemia due to ineffective erythropoiesis.

Feature	Folate (B9)	Cobalamin (B12)
Function	Transfers 1-carbon units for DNA/RNA synthesis.	Coenzyme for methionine synthase & methylmalonyl-CoA mutase.
Sources	Leafy greens (Folate from foliage).	Animal products; large hepatic stores.
Deficiency	↓ intake (alcoholism), ↑ demand (pregnancy), drugs (methotrexate).	Pernicious anemia, malabsorption (Crohn's), veganism.
Labs	↑ Homocysteine, Normal Methylmalonic Acid (MMA).	↑ Homocysteine, ↑ MMA.
Findings	Megaloblastic anemia, glossitis. NO neuro symptoms.	Megaloblastic anemia, PLUS irreversible neurological deficits.

⭐ High-Yield: Administering folate alone to a patient with combined deficiency can correct the anemia but masks the B12 deficiency, allowing progressive, irreversible neurological damage (subacute combined degeneration of the cord) to continue.

📌 Mnemonic: For B12 absorption: Intrinsic factor from Parietal cells binds B12 for absorption in the terminal Ileum.

B5, B6, B7 - The Specialists

B5 (Pantothenic Acid)
- Function: A key component of Coenzyme A (CoA) and fatty acid synthase, vital for acyl group transfer.
- Deficiency: Rare. Presents as dermatitis, enteritis, alopecia, and adrenal insufficiency.
B6 (Pyridoxine)
- Function: A crucial coenzyme for transamination (e.g., ALT, AST), decarboxylation, and heme synthesis.
- Deficiency: Sideroblastic anemia, peripheral neuropathy, seizures.
⭐ Isoniazid and oral contraceptives can lead to B6 deficiency.
B7 (Biotin)
- Function: Coenzyme for carboxylation reactions (e.g., pyruvate carboxylase).
- Deficiency: Rare. Dermatitis, alopecia. Can be induced by excessive intake of raw egg whites (avidin).

High-Yield Points - ⚡ Biggest Takeaways

B-complex vitamins are essential coenzymes in key metabolic pathways.

Thiamine (B1) deficiency in alcoholism causes Wernicke-Korsakoff syndrome.

Niacin (B3) deficiency causes Pellagra (diarrhea, dermatitis, dementia).

Folate (B9) deficiency causes megaloblastic anemia and neural tube defects.

Cobalamin (B12) deficiency causes megaloblastic anemia plus neurological deficits.

Pyridoxine (B6) deficiency can cause sideroblastic anemia and peripheral neuropathy.

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Water-soluble vitamins - B complex