Vitamin B12 and/or folate deficiency (CH) Flashcards
What is the role of vitamin B12 (cobalamin)?
RBC formation and myelination of nervous system
(Co-factor in DNA synthesis - needed for normal haematopoiesis and bone marrow function)
What is vitamin B12 also known as?
Cobalamin
Where do we get vitamin B12 from?
Animal + dairy products (meat, poultry, eggs, milk)
Where is vitamin B12 absorbed?
Terminal ileum, and requires intrinsic factor (IF)
What are the causes of vitamin B12 deficiency? (4)
- pernicious anaemia - autoantibodies against IF or gastric parietal cells and increases risk of gastric cancer - may have Hx of autoimmune disease
- post-gastrectomy
- vegan diet
- terminal ileum affected e.g. Crohn’s, Coeliac or ileocaecal resection
What is pernicious anaemia?
Autoantibodies against intrinsic factor (causing vitamin B12 deficiency) or gastric parietal cells and increases risk of gastric cancer
May have Hx of autoimmune disease
What does vitamin B12 deficiency depend on?
Stores of B12 remain in body for years, therefore deficiency depends on chronic, long-term deficiency
What does prolonged vitamin B12 deficiency lead to? (2)
- neurological disorders - dementia, sub-acute combined degeneration of spinal cord (SACD), peripheral neuropathy
- haematological disorders - megaloblastic anaemia, leukopenia, thrombocytopenia
What is folate also known as?
Vitamin B9
What is the role of folate?
DNA synthesis and amino acid metabolism
What are the sources of folate? (5)
- green leafy vegetables
- fruit
- liver
- bread
- cereal
What are the causes of folate deficiency? (4)
- malabsorption e.g. small bowel disease due to IBD or Coeliac
- malnutrition e.g. chronic alcohol use
- increased requirement e.g. pregnancy
- drug-related e.g. methotrexate (folate antagonist) or anti-epileptics
What is maternal folate deficiency associated with?
Foetal neural tube defects (NTDs) e.g. spina bifida
How does vitamin B12 vs folate deficiency generally manifest?
- B12 - megaloblastic anaemia +/- neurological and neuropsychiatric
- folate - megaloblastic anaemia without neurological signs
What are the clinical features of B12 deficiency? (4)
- anaemia signs - fatigue, pallor, SOB, glossitis & angular cheilitis (late)
- peripheral neuropathy
- tingling, numbness, paraesthesia in hands and feet
- leg weakness
- diminished proprioception and vibration sensation in feet
- dementia
- cognitive impairment
What signs of sub-acute combined spinal cord degeneration (SACD) can be seen in B12 deficiency? (3)
- ataxia
- decreased vibration sense
- positive Romberg’s test
What are the clinical features of folate deficiency? (4)
- anaemia signs - fatigue, pallor, SOB, glossitis & angular cheilitis (late signs)
- loss of appetite and weight loss - hallmark of folate deficiency, WL due to both loss of appetite and increased energy demands of ineffective erythropoiesis
- Sx of underlying causes e.g. prolonged diarrhoea in IBD/Coeliac
- foetal spina bifida (neural tube defect) - if maternal deficiency
What can pernicious anaemia (B12 deficiency) present? (7)
- gastric pain/discomfort
- tiredness
- dyspnoea
- paraesthesia
- sore red tongue
- diarrhoea
- mild jaundice
What are the risk factors for B12 deficiency? (7)
- age>65
- gastric surgery (bypass/resection)
- chronic GI disease
- vegan/strict vegetarian diet
- metformin use
- H2 receptor antagonist or PPI
- pernicious anaemia
What are some risk factors for folate deficiency? (7)
- age>65
- low dietary folate intake
- intestinal malabsorptive disorders (Crohn’s, Coeliac, bacterial overgrowth syndrome)
- alcohol-use disorder
- pregnant or lactating
- drugs - methotrexate, trimethoprim, sulfasalazine, pyrimethamine, anticonvulsants e.g. phenytoin
- congenital defects in folate absorption and metabolism
What are the first-line investigations for B12 and folate deficiency?
- FBC - useful for severe and prolonged deficiency (macrocytic anaemia, high MCV, low Hct, may present as part of pancytopenia)
- peripheral blood smear - megalocytes, hypersegmented poly-morphonucleated cells
- serum vitamin B12
- reticulocyte count - differentiate B12 deficiency from haemolytic anaemia, if low –> decreased production (vs high in HA)
What does FBC show in B12/folate deficiency? (4)
- macrocytic anaemia
- high MCV
- low Hct
- may present as part of pancytopenia
What would a blood film show in B12 and folate deficiency?
Macrocytic megaloblastic anaemia - decreased Hb, increased MCV, hyperchromic RBCs, hypersegmented neutrophils
What is reticulocyte count like in B12 and folate deficiency?
Low count (indicates decreased production) - distinguishes deficiencies from haemolytic anaemia
What serum vitamin B12 levels indicate deficiency?
- <148 picomols/L (<200 picograms/mL) = probable deficiency
- 148-258 picomols/L (201-350 picograms/mL) = possible deficiency
- > 258 picomols/L (>350 picograms/mL) = unlikely deficiency
How do we test for pernicious anaemia (B12 deficiency)?
Test for autoantibodies: anti-IF (more specific), anti-GPC
What tests may help diagnose B12 deficiency at an early, asymptomatic state?
Methylmalonic acid and homocysteine levels
What do homocysteine levels show in B12 and folate deficiencies?
Elevated in both
What does methylmalonic acid show in B12 and folate deficiencies?
Elevated in B12 deficiency and normal in folate deficiency
What is holotranscobalamin like in B12 deficiency?
B12 bound to transcobalamin = low
How do we manage vitamin B12 deficiency?
-
IM supplementation of B12 (hydroxycobalamin) - lifelong
- if mild/ASx etc - oral cyanobobalamin/hydroxycobalamin
- dietary supplementation of B12 + multivitamins - especially in older patients with poor diets
How do we manage folate deficiency?
Oral folate (folic acid) supplementation, nutritional counselling to increase folate intake
Why is folic acid given to pregnant women?
Risk of neural tube defects e.g. spina bifida and anencephaly if maternal folate deficiency
400mcg of folic acid until 12th week of pregnancy
Why do we always replace B12 before folate (BeFore)?
Protects against sub-acute combined degeneration of spinal cord:
- ataxia
- positive Romberg’s test
- distal sensory loss, impaired proprioception and vibration
- hyperreflexia
- absent ankle jerks/extensor plantars
- tingling
What are some complications of B12 deficiency?
- neurological - cognitive, myelopathy (SC disease), neuropathy, SACD
- haematological - anaemia, leukopenia, thrombocytopenia
- low birth weight + preterm delivery
