Vitamin
B12 (cobalamin) deficiency
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Vitamin B12 |
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- Clinical
features
- Polyneuropathy
- Sensory D: 2ƒ spinal or peripheral nerve
lesions
- Early: Paresthesias
- Loss especially of
large fiber modalities
- Distal
- Motor: Later
in course; Distal
- Reflexes
- Tendon: Reduced
or absent at ankles
- Plantar: Upgoing
- Autonomic: Postural
hypotension
- CNS
- Spinal cord: Earliest
locus of involvement
- Major cause of
sensory & motor disability
- Posterior column
fiber loss
- Spasticity in
legs
- Similar clinical
features to N2O toxicity
- Other CNS
- Cognitive impairment
in adults: Leukoencephalopathy on MRI
- Mental retardation
or encephalopathy in childhood syndromes
- Sensory:
Reduced smell & taste
- Gait ataxia
- Anemia: Megaloblastic;
Due to reduced DNA synthesis
- Gastrointestinal:
Glossitis; Diarrhea
- Fingernails:
Hyperpigmented
- Testing
- Serum
- Low B12
- Clinically
significant: < 100 pg/ml
- Suspicious: < 200
pg/ml
- High homocysteine
& methymalonic acid
- Confirm biological
significance of low B12 levels
- MRI
- Hyperintense T2
lesions in posterior columns (50%)
- Lesions resolve after
8 to 12 months of therapy
- Evoked potentials
- Somatosensory:
Abnormal tibial & median
- Motor: Normal in most
- Pathology
- Spinal cord
- Multifocal axonal
loss & demyelination
- Localization
- Cervical &
thoracic
- Posterior column
> Anterolateral & Anterior
- Peripheral nerve:
Axonal loss; Occasional ± demyelination
- Treatment: 1 mg i.m. q 3
months
- Prognosis: Stabilization, or
Some improvement
- Paresthesias
- Resolve within weeks
- Rarely transient
exacerbation after treatment
- Myelopathy changes
slowly if at all
- Causes of B12
deficiency: Normal body stores last 3 to 4 years
- Gastrointestinal
malabsorption
- Deficient intrinsic
factor production
- Post-gastrectomy
- Antibody vs parietal
cells: Pernicious anemia
- Onset: Median = 60
years; Female slightly > Male
- Antibody targets:
Gastric H+/K+-ATPase
- Catalytic a subunit, and
- Glycoprotein b subunit
- Regions of stomach
affected: Fundus & body; Not antrum
- Mechanisms of B12
deficiency
- Reduced intrinsic
factor production 2ƒ parietal cell loss
- Antibodies to B12
binding site on intrinsic factor: Prevent formation of complex that
is normally carried to terminal ileum & absorbed
- Associated immune
disorders: Thyroiditis; Diabetes; Addison's; Ovarian failure; 1ƒ
hypoparathyroidism; Graves; Vitiligo; Myasthenia gravis; Lambert-Eaton
syndrome; Common variable immunodeficiency with low Ig or IgA (younger
patients)
- Associated
neoplasia: Gastric carcinoma (1% to 3%)
- Family history: 20%
of relatives also have pernicious anemia; Especially 1st degree
females
- Gastritis
treatment: Corticosteroids; Azathioprine
- No digestion of
cobalamin-R-binder complex
- Pancreatic
insufficiency
- Consumption of
cobalamin in GI tract
- Intestinal bacterial
overgrowth
- Poor absorption by
distal ileum
- Sprue-related
disorders
- Autosomal recessive
disorders
Anemia; Proteinuria; Juvenile onset
- Parasitic infection: Diphyllobothrium
latum
- Dietary inadequacy in
vegetarians
- Sources: Meat &
dairy products
- Congenital disorders
of B12 binding proteins
- Vitamin B12
R-binding protein deficiency
- Neurological B12
deficiency syndromes in adults
- Gastric intrinsic
factor deficiency
- Congenital anemia
& jaundice
- Transcobolamin II
deficiency
- Megaloblastic
anemia; Diarrhea; Immunodeficiency; Mental retardation
- Abnormalities of
synthesis of active forms of B12
- Methylcobalamin
deficiency, types E and G
- Neurological (CNS)
& hematological B12 deficiency syndromes
- In children
- Adenosylcobalamin
deficiency
- Episodic
ketoacidosis; Encephalopathy; Neutropenia; Osteoporosis
- Combined
methylcobalamin & adenosylcobalamin deficiency
- Types I and II
- Mental retardation;
anemia; ± myelopathy in slowly progressive cases
- Nitrous oxide
exposure
1. Oxidizes
cobalt in cobolamin: Methylcobalamin inactivated
2. Inhibits
conversion of homocysteine to methionine:
3. Reduced
supply of S-adenosylmethionine
- Abnormal release of B12
from lysosomes