Vitamin B12 deficiency, typically found in older adults and vegetarians, is characterised by ineffective erythropoiesis and neurological changes, megaloblastic anaemia, subacute combined degeneration of the spinal cord and non-specific white matter changes.
Description
Vitamin B12 deficiency is a common nutritional deficiency characterised by reduced serum levels of cobalamin, essential for DNA synthesis and cell division. This deficiency is particularly significant due to its potential for irreversible neurological damage, manifesting in the form of subacute combined degeneration of the spinal cord, and cognitive impairment.
Pathogenesis
Vitamin B12, also known as cobalamin, plays a crucial role in DNA synthesis, red blood cell production, and neurological function. It is mainly derived from animal products, hence deficiency is common in individuals adhering to a vegan or vegetarian diet. Pernicious anaemia, an autoimmune condition affecting B12 absorption in the gut, is also a significant cause. Deficiency in B12 leads to ineffective erythropoiesis resulting in megaloblastic anaemia and neuropsychiatric symptoms due to disruption of the methylation process in the CNS.
Subtypes
While there are no established subtypes of vitamin B12 deficiency, the manifestation of the deficiency can vary, resulting in different clinical syndromes including:
- Pernicious anaemia
- Subacute combined degeneration of the spinal cord
- B12 deficiency-related neuropathy
Epidemiology, Risk Factors & Associations
- Older age (prevalence is 5-15% in adults >65 years)
- Vegetarian or vegan diet (50% prevalence in long-term vegans)
- Autoimmune diseases, particularly pernicious anaemia (75% cases of B12 deficiency in adults)
- Gastric surgery, e.g., bariatric surgery (common in post-gastric surgery patients)
Clinical Features
The clinical manifestations of B12 deficiency include:
- Anaemia-related symptoms, e.g., fatigue, pallor
- Neurological symptoms such as paraesthesia, unsteady gait
- Cognitive changes ranging from memory impairment to dementia
- Glossitis (inflamed tongue)
Complications
- Neurological complications: irreversible cognitive impairment, subacute combined degeneration of the spinal cord
- Haematological complications: severe anaemia
- Pregnancy-related complications: neural tube defects in newborns
Pathological Features
Histopathology
- Macroscopic: Pale, enlarged cells
- Microscopic: Megaloblastic erythropoiesis, hypersegmented neutrophils
Serology
- Low serum B12 levels
- Elevated methylmalonic acid and homocysteine levels
Biochemistry
- Macrocytic anaemia on full blood count
Radiological Features
Vitamin B12 deficiency does not have specific radiological signs; however, it can demonstrate various non-specific findings, particularly in the brain and spinal cord.
General Features
- Non-specific white matter changes
- Atrophy in severe and prolonged cases
- MRI is the modality of choice for imaging the spinal cord and brain.
MRI
Brain
- T1: Non-specific white matter changes, potential atrophy in prolonged deficiency
- T2/FLAIR: Hyperintensities in white matter, possibly reflecting demyelination or axonal loss
- DWI/ADC: No specific diffusion restrictions are expected
- T1 Gad+: No enhancement expected unless there is associated pathology
Spine
- T1: Hyperintense signal in dorsal columns of the spinal cord (subacute combined degeneration)
- T2: Hyperintense signal in dorsal columns of the spinal cord
Grading and Staging
There is no established grading or staging system for vitamin B12 deficiency.
Diagnosis
The diagnosis of B12 deficiency is typically based on a combination of clinical findings, biochemical tests demonstrating low serum B12 levels and macrocytic anaemia, and response to treatment.
Differential Diagnosis
- Folate deficiency: similar clinical and haematological findings but typically no neurological manifestations
- Hypothyroidism: can present with fatigue and cognitive changes
- Normal ageing: may mimic the cognitive changes seen in B12 deficiency, but no accompanying haematological findings.
Management
Initial management includes supplementation of B12, usually via intramuscular injections. Referral to haematology is typical for further evaluation and management of associated anaemia, while neurology input may be necessary for associated neurological complications.