B12 and Folate deficiency

Question 1

What is the most common cause of B12 deficiency in the UK? What is the pathology?

Answer 1

Pernicious anaemia

Autoimmune condition:

• Destruction of parietal cells in stomach/antibodies to intrinsic factor itself
• Leading to a reduction in the production of intrinsic factor - secreted by parietal cells in the gastric mucosa
• Intrinsic factor is essential for absorbing B12 in the terminal ileum

Usually develops in >50yrs, F>M, FHx +ve, other autoimmune diseases e.g. thyroid, Addison’s, vitiligo

Question 2

What are some other causes of B12 deficiency?

Answer 2

Drugs:

• Colchicine
• Metformin
• Nitrous oxide
• PPIs
• H2-receptor antagonists

Gastric:

• Total/partial gastrectomy
• Congenital intrinsic factor deficiency/abnormality

Intestinal:

• Malabsorption e.g. coeliac disease
• Ileal resection
• Crohn’s
• Tapeworm infection

Nutritional:

• Malnutrition
• Vegan diet

Question 3

What are some causes of folate deficiency?

Answer 3

• Dietary intake
• Malabsorption
• Drugs - allopurinol, anticonvulsants, nitrofurantoin, sulfasalazine, methotrexate
• Excessive requirements in: pregnancy, malignancy, blod disroders
• Excessive urinary excretion
• Liver disease

Question 4

How do you investigate B12/folate deficiency

Answer 4

Bloods:
- FBC - Macrocytic (MCV >100fl)

• Blood film (Large cells with immature nuclei due to defective DNA synthesis)
• Serum concentrations of cobalamin and folate
• Anti-intrinsic factor antibodies
• Anti-endomysial or anti-transglutaminase antibodies (to exclude coeliac)

Question 5

How do you manage B12 deficiency?

Answer 5

Drug: Hydrooxocobalabin

• Loading dose - IM 1mg 3x/wk for 2/52
• Maintenance - IM 1mg every 3/12 for life (if NOT dietary; PO cyanocobalamin or 2x yrly 1mg injection (if dietary related)

If neurological involvement: - Urgent referral to haematology

Question 6

How do you manage folate deficiency?

Answer 6

Drug: Folic acid

• 5mg PO OD for 4/12, possibly for life
• Pregnancy: standard advice = 400mcg every day before conception up to 12wks post; 5mg if high risk

Dietary advice:

• Broccoli
• Sprouts
• Asparagus
• Peas
• Chickpeas
• Brown rice

Question 7

What follow up for pernicious anaemia is required?

Answer 7

TFTs might be performed - as coexisting thyroid disease (as autoimmune) is common

More mindful of GI symptoms e.g. indigestion/stomach pain - as increases the risk of gastric cancer by 2-3x

Question 8

What are some complications of B12 and folate deficiency?

Answer 8

B12:
- Vision problems
- Memory loss/dementia
- Ataxia
- Peripheral neuropathy (esp. legs, also autonomic)
- Parasthesia
(most neurological problems are irreversible)
- Infertility (reversible)
- Neural tube defects (if pregnant)
- Stomach cancer (if pernicious anaemia cause)

Folate:

• Infertility (reversible)
• Cardioascular disease
• (colon) cancers
• Premature birth/low birth weight/neural tube defects