A 58-year-old vegetarian woman from rural India presents with progressive fatigue, dyspnea on exertion, and paresthesias in both feet for 3 months. On examination, she has glossitis, angular cheilitis, and a positive Romberg test. Blood investigations show hemoglobin 7.2 g/dL, MCV 118 fL, and reticulocyte count 0.8%. Peripheral blood smear reveals hypersegmented neutrophils and macro-ovalocytes. Serum vitamin B12 level is 95 pg/mL (normal 200). What is the most likely diagnosis?

Question

A 58-year-old vegetarian woman from rural India presents with progressive fatigue, dyspnea on exertion, and paresthesias in both feet for 3 months. On examination, she has glossitis, angular cheilitis, and a positive Romberg test. Blood investigations show hemoglobin 7.2 g/dL, MCV 118 fL, and reticulocyte count 0.8%. Peripheral blood smear reveals hypersegmented neutrophils and macro-ovalocytes. Serum vitamin B12 level is 95 pg/mL (normal >200). What is the most likely diagnosis?

Accepted Answer

A. Megaloblastic anemia due to vitamin B12 deficiency. ## Clinical Diagnosis

**Key Point:** This patient has megaloblastic anemia with confirmed vitamin B12 deficiency (serum B12 95 pg/mL) and neurological manifestations (paresthesias, positive Romberg test) pathognomonic for B12 deficiency.

## Diagnostic Features

| Feature | Finding | Significance |
|---------|---------|---------------|
| MCV | 118 fL | Macrocytic (>100 fL) |
| Peripheral smear | Hypersegmented neutrophils, macro-ovalocytes | Megaloblastic pattern |
| Serum B12 | 95 pg/mL | Frankly low (<200 pg/mL) |
| Neurological signs | Paresthesias, positive Romberg | B12-specific (not seen in folate deficiency) |
| Reticulocyte count | 0.8% | Inappropriately low for degree of anemia |
| Dietary history | Vegetarian | Risk factor for B12 deficiency |

## Pathophysiology of B12 Deficiency Anemia

1. **DNA synthesis impairment**: B12 (as methylcobalamin) is essential for methionine synthase, which converts homocysteine to methionine. Without adequate B12, deoxyribonucleotide synthesis fails.
2. **Nuclear-cytoplasmic asynchrony**: Cytoplasm matures normally while nuclear maturation lags, producing large cells with immature chromatin pattern (megaloblasts).
3. **Neurological damage**: B12 deficiency impairs myelin synthesis via methylmalonyl-CoA mutase pathway, causing subacute combined degeneration (SCD) — posterior and lateral column disease.

**High-Yield:** Neurological manifestations (paresthesias, ataxia, positive Romberg) are **SPECIFIC to B12 deficiency** and do NOT occur in folate deficiency alone. This is the key discriminator.

## Why B12 Deficiency in This Patient

- **Vegetarian diet** (no animal products = no B12 source)
- **Serum B12 definitively low** (95 pg/mL)
- **Neurological signs present** (folate deficiency does not cause myelopathy)
- **Hypersegmented neutrophils** (classic for megaloblastic anemia)

**Clinical Pearl:** In India, dietary B12 deficiency is common among vegetarians and vegans. Pernicious anemia (autoimmune) is less common but must be ruled out with intrinsic factor antibodies if dietary intake is adequate.

## Management Approach

```mermaid
flowchart TD
  A[Macrocytic anemia + low B12]:::outcome --> B{Neurological signs?}:::decision
  B -->|Yes| C[B12 deficiency anemia]:::outcome
  B -->|No| D[Folate deficiency or other cause]:::outcome
  C --> E{Cause of B12 deficiency?}:::decision
  E -->|Dietary| F[Vegetarian/vegan diet]:::action
  E -->|Malabsorption| G[Pernicious anemia, post-gastrectomy]:::action
  F --> H[B12 supplementation: IM injections or oral]:::action
  G --> I[IM B12 injections preferred]:::action
```

**Mnemonic: NEUROLOGICAL B12 — N.E.U.R.O.L.O.G.I.C.A.L = Never Expect Usual Reversibility Of Loss; Only Gradual Improvement; Lasting Axonal damage**
- Neurological damage can be **irreversible** if B12 replacement is delayed >6 months.
- Early treatment prevents permanent myelopathy.

[cite:Robbins 10e Ch 14]

![Megaloblastic Anemia diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/2618.webp)

Answer

B. Macrocytic anemia due to hypothyroidism

Answer

C. Sideroblastic anemia with neurological manifestations

Answer

D. Megaloblastic anemia due to folate deficiency

Explanation

Clinical Diagnosis

Diagnostic Features

Pathophysiology of B12 Deficiency Anemia

Why B12 Deficiency in This Patient

Management Approach

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Feature	Finding	Significance
MCV	118 fL	Macrocytic (>100 fL)
Peripheral smear	Hypersegmented neutrophils, macro-ovalocytes	Megaloblastic pattern
Serum B12	95 pg/mL	Frankly low (<200 pg/mL)
Neurological signs	Paresthesias, positive Romberg	B12-specific (not seen in folate deficiency)
Reticulocyte count	0.8%	Inappropriately low for degree of anemia
Dietary history	Vegetarian	Risk factor for B12 deficiency