TABLE 2.

Formulation and dosage regimes for treatment of vitamin B12 deficiency, subdivided into congenital and acquired causes. Abbreviations: OH-Cbl, hydroxocobalamin; CN-Cbl, cyanocobalamin.

Congential	Acquired
Cobalamin-binding intrinsic factor deficiency (CBLIF)	British National Formulary
• 1 mg IM OH-CbI/CN-Cbl daily in severe pancytopenias until resolved and then spaced out according to metabolic parameters	• Inpatients without neurological involvement: 1 mg IM OH-Cbl 3 times a week for 2 weeks and then maintenance 1 mg IMOH-Cbl every 3 months
	• Inpatients with neurological involvement, Img IMOH-Cbl on alternate days until there is no clinical improvement and then maintenance 1 mg IM OH-Cbl every 2 months
• Eventually patients stabilized on twice yearly 1 mg CN-Cbl or OH-Cbl injections	• 50 μg low-dose CN-Cbl in asymptomatic, borderline cases
Imerslund-Grasbeck Syndrome (IGS)	British Columbia Medical Association
• 1 mg IM OH-CbI daily for 10 days and then once a month for lifetime OR	• For pernicious anemia or food-bound cobalamin malabsorption, 1 mg daily oral CN-Cbl.
• 1 mg IM OH-CbI/CN-CbI daily in severe pancytopenia until resolved and then spaced out according to metabolic parameters	• Inmost other cases a dose of 250 μg/day may be used
• Eventually patients stabilized on twice yearly 1 mg CN-Cbl or OH-Cbl injections with careful monitoring	• Reserve parenteral administration for those with neurological symptoms:
	• IM/SC 1 mg IM CN-Cbl OD for 1–5 days, followed by 1-2 mg OD oral CN-Cbl.
	• Ensure serum Cbl normalized after 4–6 months
Cobalamin Defects	Netherlands
• 1 mg IM OH-CbI daily, with frequency of administration individually titrated according to metabolic response OR	• Dutch Organization of General Practitioners 2014 viewpoint: Treat a cobalamin count below 148 pmol/L and clinical symptoms with 11 mg daily oral Cbl
• Loading dose of 0.5–1 mg daily IMOH-Cbl or CN-Cbl for 4–8 weeks then maintenance of 0.5–1 mg weekly OH-Cbl	• Dutch Healthcare institute Pharmacotherapeutic Compass: IM/SC loading dose of 10 injections of 1 mg OH-Cbl at intervals of ≥3 days; maintenance dose 1 mg once every 2 months or 300 ug/month, for lifelong supplementation if underlying cause not removed
	• In case of evident neurological disorders: 1 mg once or twice a week for 2 years.
Transcobalamin II deficiency	France
• IM administration of 1 mg of OH-Cbl or CN-Cbl weekly for lifetime	• CARE B12 research group recommendations:
	• Inpernicious anaemia: 1 mg oral CN-Cbl daily for life OR 1 mg IMCN-Cbl daily for 1 week then ‘once weekly for 1 month then monthly for life
	• 1–2 mg per day for at least 2–3 months in cases of moderate to severe neurological manifestations
	• In food-bound cobalamin malabsorption, Crohn's disease, malabsorption or dietary deficiency: 1 mg oral CN-Cbl daily for 1 month then 125 μg–1 mg daily CN-Cbl until cause is corrected OR 1 mg IM CN-Cbl daily for 1 week then once weekly for 1 month then per month for 1–3 months until cause is corrected
	• 1 mg daily for 1–3 months in cases of severe neurological manifestations
Haptocorrin deficiency	Australia
• Treatment not indicated	• Royal Children’s Hospital (Melbourne), Immigrant Health Service—varying regimens
	• For infants with clinical deficiency: 250 μg–1 mg IM OH-Cbl (preferred) or CN-Cbl on alternate days for 1–2 weeks then 250 μg IM weekly, switch to oral when child is well
	• For older children with mild disease, 1 mg oral daily
	• Insub-clinical cases or with dietary deficiency, 50–200 jug oral daily