Can Slow Gait, Slow Speech, and Fatigue Be Caused by Pernicious Anemia?
Yes, pernicious anemia can absolutely cause slow gait, slow speech, and fatigue in older adults, particularly those with gastrointestinal disorders or autoimmune conditions, and should be actively investigated as these neurological manifestations may become irreversible if treatment is delayed beyond 3 months. 1
Why Pernicious Anemia Causes These Symptoms
Pernicious anemia results from autoimmune destruction of gastric parietal cells, leading to intrinsic factor deficiency and subsequent vitamin B12 malabsorption. 2, 3 The resulting cobalamin deficiency produces:
- Neurological damage: Vitamin B12 deficiency allowed to progress beyond 3 months produces permanent degenerative lesions of the spinal cord, including subacute combined degeneration of the posterior columns. 1, 4
- Motor impairments: Gait disturbances, muscle stiffness, and slowed movements occur due to neurological involvement. 5
- Cognitive slowing: Brain fog, difficulty concentrating, and mental fatigue manifest as slow speech and processing. 5
- Profound fatigue: General fatigue, decreased appetite, and weakness are hallmark presentations. 6
High-Risk Patient Profile
You should have heightened suspicion in older adults with:
- Gastrointestinal disorders: Celiac disease, inflammatory bowel disease, or history of gastric surgery all impair B12 absorption. 5, 1
- Autoimmune conditions: Type 1 diabetes, autoimmune thyroid disease, and vitiligo strongly associate with pernicious anemia, with 28-68% of thyroid disease patients having B12 deficiency. 7
- Age over 50-60 years: This is the typical age of onset, though cases in the very elderly (>90 years) occur. 6, 4
Essential Diagnostic Workup
Immediate laboratory testing should include:
- Complete blood count: Look for macrocytic anemia (MCV >100 fL) and pancytopenia. 6, 3
- Serum B12 level: If <180 pg/mL, confirm deficiency and proceed to etiology testing. 7
- Methylmalonic acid (MMA): For indeterminate B12 levels (180-350 pg/mL), MMA has 98.4% sensitivity for functional deficiency. 7
- Autoantibodies: Parietal cell antibodies (97% positive) and intrinsic factor blocking antibody (52% positive) confirm autoimmune etiology. 4
- Fasting gastrin: Markedly elevated (mean >1,500 pg/mL) in pernicious anemia. 4
Additional investigations for fatigue should include: 5
- Iron studies and ferritin (iron deficiency commonly coexists)
- Thyroid function tests
- Vitamin D levels
- Electrolytes
- Inflammatory markers (ESR, CRP)
Critical Treatment Principle
Begin intramuscular B12 immediately if neurological symptoms are present, even before antibody results return, as delays can result in irreversible spinal cord damage. 7 The FDA-approved indication for cyanocobalamin injection specifically includes pernicious anemia with associated gastrointestinal pathology. 1
- Patients require monthly B12 injections for life. 1
- Failure to treat results in return of anemia and incapacitating, irreversible nerve damage. 1
- Oral B12 is ineffective in pernicious anemia due to intrinsic factor deficiency. 1
Common Pitfalls to Avoid
Never give folic acid without B12 replacement. Doses of folic acid >0.1 mg daily may produce hematologic remission while allowing neurological damage to progress unchecked. 1 This masks the true diagnosis while permitting irreversible spinal cord injury.
Do not delay treatment for confirmatory testing. If clinical suspicion is high with macrocytic anemia and neurological symptoms, start B12 immediately. 7
Do not assume other causes explain all symptoms. While fatigue in gastrointestinal disease is multifactorial, B12 deficiency is a readily treatable contributor that must be identified. 5
Long-Term Surveillance
Patients with pernicious anemia have 3 times the incidence of gastric carcinoma compared to the general population. 1 They also develop gastric neuroendocrine tumors in approximately 18% of cases. 4 Appropriate endoscopic surveillance should be performed when indicated. 1, 4