Makindo Medical Notes

Neurological signs of B12 deficiency can be present even without anaemia. There is a 1-2% risk of thyroid disease or Gastric cancer. Pernicious anaemia is best confirmed with anti-intrinsic factor testing; anti-parietal cell antibody test is inferior.

About

• Autoimmune cause of B12 deficiency leading to haematology and neurology problems
• Increased risk of Gastric cancer

Aetiology

• The gastric parietal cells that produce Intrinsic factor and H⁺ions are destroyed
• Possibly by an autoimmune inflammatory process which interestingly can be reversed by steroids

Physiology

• Normal diet has 20 ug of B12 per day and the daily requirement is 1-2 ug/day
• B12 binds to the Intrinsic factor and is absorbed in the terminal ileum
• Absorbed and bond to transcobalamin 2 in the portal circulation
• Stored then in the liver enough to last 2-4 years
• B12 converts Homocysteine to methionine

Clinical

• Mean age = 60, fair skin, blue eyes
• Mild splenomegaly and pallor
• Vitiligo and increased incidence of organ-specific endocrine diseases e.g. Addison's diseaseand thyroid disease.
• Painful raw beefy tongue is classical - glossitis for B12 deficiency

Neurological Signs of B12 deficiency

• Optic atrophy and retinal haemorrhage
• Dementia
• Polyneuropathy - paraesthesia and distal sensory loss with absent ankle jerk
• Dorsal column vibration and proprioception loss
• Corticospinal loss - extensor plantars and ++ Knee jerk
• Spinal cord damage is irreversible

Investigations

• FBC: Hb can be 4-5 g/dL but often well tolerated. Macrocytic anaemia MCV >110 fL. Anisopoikilocytosis Hypersegmented neutrophils, and low WCC and platelets
• Low Serum B12 (NR 160–960 ng/L).
• Serum Folate may be low (NR 4.0–18.0 µg/L)
• Exclude Iron deficiency Ferritin
• Check for Intrinsic Factor Antibody (IFAB) is notoriously insensitive as it only comes back positive in around 50% of patients with PA. If the test comes back positive for the IF antibodies then the patient will have PA. However, if negative they can still have PA. A negative test-result can not rule out PA. Retesting patients who have previously tested positive is not needed. Those with IFAB should have lifelong therapy with cobalamin. Patients negative for IFAB should have lifelong therapy in the presence of an objective clinical response.
• Unconjugated hyperbilirubinemia and Raised LDH
• Low reticulocytes (ineffective erythropoiesis)
• Endoscopy - Atrophic gastritis with Achlorhydria (Reduced HCl) develops along with macrocytic anaemia. Duodenal biopsies to exclude Coeliac.
• Many centres don't bother with a Schilling test and rely on biochemical evidence of B12 deficiency and antibodies to Parietal cells and Intrinsic factor for the diagnosis
• Bone marrow: rarely done but shows megaloblastic erythropoiesis

Differential

• Gastrectomy
• Atrophic gastritis
• Terminal ileal disease
• Diet e.g. vegans

Management

• Avoid blood transfusion unless very compromised as there is a risk of volume overload and acute left ventricular failure. If needed give diuretic cover and monitor closely.
• One does not need to delay treatment before doing a Schilling test as the test is one of uptake and actually, a dose of B12 is given to saturate metabolism
• If folate deficiency never give folate alone because, although it might partially correct the blood abnormalities associated with vitamin B12 deficiency, it will also cause the B12 level to drop even further and might precipitate severe neuropathy.
• Give Vitamin B12 (Hydroxocobalamin) 1 mg twice a week IM for 3 weeks and then 1 mg every 3 months for life. May also require additional haematinics such as folate 5 mg OD
• Three things can happen due to the sudden burst in haemopoiesis when treatment is started with B12 (folate may also be given) and then they improve
  • Hypokalaemia
  • Reticulocytosis
  • An initial drop in Hb
• Ensure that the person is replete with iron and folate before starting therapy. The reticulocyte count should rise in 2-3 days