Four Stages of Vitamin B12 Deficiency

1. Serum B12 concentration low; no clinical or metabolic abnormalities. Low plasma level of holotranscobalamin
2. plasma and cells stores B12 become depleted. Serum B12 is low with metabolic abnormalities
3. Increased level of HCY and MMA and low holotranscobalamin–low B12 level. Damaged metabolism, dU suppression is abnormal. Neuro-Psychiatric symptoms with mild haematological changes without anaemia
4. Clinical signs become recognisable (Addisonian criteria)
   • Macro Ovalocytosis
   • Elevated MCV or Erythrocytosis
   • Lowered haemoglobin
   • Patients presenting with the classical features of pernicious anaemia (PA) would therefore be expected to have progressed through stages I II & III over several years. Some vegans and patients with malabsorption of food cobalamin, may also progress through these stages. Sometimes over many years, but others may not progress beyond stage I or II. These considerations imply that there are many more individuals in stages I, II, & III of B12 Deficiency than in stage IV (PA).
   • Low nutritionalintake of Vitamin B12 may lead to negative balance and finally to functional deficiency when tissue stores of Vitamin B12 are depleted.
   • Early Diagnosis (stage I & II) of Vitamin B12 Deficiency seems to be useful because irreversible neurological damage may be prevented by cobalamin substitution.