Vitamin B12 Deficiency - Hyperexcision

Vitamin B12 (cobalamin) deficiency is classically seen in chronic alcoholism, malnutrition, and strict vegetarians. Vitamin B12 is required for folate metabolism, DNA/RNA synthesis, succinyl-CoA synthesis (for haemoglobin), and myelination.

Difference between Folate and B12 deficiency

	Folate deficiency	B12 deficiency
Peripheral neuropathy	Absent	Present
Ataxia	Absent	Present
Subacute combined degeneration	Absent	Present
Serum methylmalonic acid	Normal	Elevated
Urine Methylmalonic acid	Normal	Elevated
Serum homocysteine	Elevated	Elevated

Causes of vitamin B12 deficiency
- Inadequate dietary intake
  - Vegetarian diet
- Malabsorption
  - Pernicious Anemia
  - Atrophic Gastritis
  - Achlorhydria
  - Gastrectomy/ Bariatric surgery
  - Pancreatic insufficiency
  - Terminal ileal resection
  - Crohn’s disease
  - Diphyllobothrium latum infection
- Increased requirement
  - Pregnancy
  - Breastfeeding
  - Hyperthyroidism
  - AIDS
  - Alpha thalassaemia
- Drug induced
  - Nitrous oxide
  - Metformin use for > 4 months
  - Proton pump inhibitor use for > 1 year
- Congenital causes
  - Inborn errors of metabolism
  - Transcobalamin-II deficiency
  - Imerslund-Gra
Signs and symptoms
- Symptoms of anaemia
- Angular cheilitis
- Glossitis
- Atrophy of papillae
- Anoresixia
- Weight loss
- Vitiligo
- Peripheral neuropathy
  - Glove and stocking distribution of pain and numbness (paraesthesia)
  - Nerve damage due to vitamin B12 deficiency si permanent
- Subacute Combined Degeneration
  - Decreased deep tendon reflexes
  - Decreased vibration sense
  - Positive Babisnki
  - Paraesthesia
  - Psychiatric manifestations
- Cognitive impairment
  - Memory loss
  - Depression
  - Irritability
- Ataxia
- Atherosclerosis due to increased homocysteine levels,
  - Increases the risk for thrombosis and myocardial infarction
Differentials
- Folate deficiency
- Iron deficiency anaemia
- Myelodysplastic syndrome
Investigations
- Complete blood count
  - Low haemoglobin
  - Low haematocrit
  - High MCV
  - Low reticulocyte count
  - Leukopaenia
  - Thrombocytopaenia
- Peripheral blood film
  - Hypersegmented neutrophils
  - Oval megalocytes
  - Circulating megaloblasts
- Serum B12 levels
  - May be normal or abnormal
- Serum methylmalonic acid
  - Elevated
- Serum homocysteine levels
  - Elevated
- Lactate dehydrogenase
  - Elevated
- Holotranscobalamin is useful for identifying cobalamin deficiency in alcoholic patients
- Anti-parietal cell antibodies and anti-intrinsic factor antibodies for pernicious anaemia
- MRI of the brain and spinal cord
  - Severe demyelination of the dorsal and lateral columns
  - Inverted V sign
  - Pairs of binocular sign
  - Dot signs
- The schilling test is no longer performed
Treatment
- Increase consumption of foods rich in vitamin B12: eggs, meat, dairy products, fish, and cobalamin-fortified foods
- Intramuscular (or oral) vitamin B12
  - Regimens vary depending on whether there is neurological involvement. It improves neuropathy within the first 3 – 6 months, but has little effect on cord signs.
  - B12 deficiency is treated first in patients with concurrent folate deficiency to avoid masking and precipitating subacute combined degeneration.
Complications
- Gastric cancer in patients with pernicious anaemia
- Poor obstetric outcomes
  - Spontaneous abortion
  - Intrauterine growth restriction
  - Low birth weight
  - Neural tube defects
- Temporary infertility

Reference Intervals ›

Biochemistry

ACTH	P: <80 ng/L
ALT	P: 5–35 U/L
Albumin	P: 35–50 g/L
Aldosterone	P: 100–500 pmol/L
Alk. phosphatase	P: 30–130 U/L
α-Amylase	P: 0–180 IU/dL
α-Fetoprotein	S: <10 kU/L
Angiotensin II	P: 5–35 pmol/L
ADH	P: 0.9–4.6 pmol/L
AST	P: 5–35 U/L
Bicarbonate	P: 24–30 mmol/L
Bilirubin	P: 3–17 μmol/L
BNP	P: <50 ng/L
CRP	P: <10 mg/L
Calcitonin	P: <0.1 mcg/L
Calcium (ionized)	P: 1.0–1.25 mmol/L
Calcium (total)	P: 2.12–2.60 mmol/L
Chloride	P: 95–105 mmol/L
Cholesterol	P: <5.0 mmol/L
VLDL	P: 0.128–0.645 mmol/L
LDL	P: <2.0 mmol/L
HDL	P: 0.9–1.93 mmol/L
Cortisol AM	P: 450–700 nmol/L
Cortisol Midnight	P: 80–280 nmol/L
CK ♂	P: 25–195 U/L
CK ♀	P: 25–170 U/L
Creatinine	P: 70–100 μmol/L
Ferritin	P: 12–200 mcg/L
Folate	S: 2.1 mcg/L
FSH	P: 2–8 U/L ♂; >25 menopause
GGT ♂	P: 11–51 U/L
GGT ♀	P: 7–33 U/L
Glucose (fasting)	P: 3.5–5.5 mmol/L
Growth hormone	P: <20 mu/L
HbA1C (DCCT)	B: 4–6%
HbA1C (IFCC)	B: 20–42 mmol/mol
Iron ♂	S: 14–31 μmol/L
Iron ♀	S: 11–30 μmol/L
Lactate (venous)	P: 0.6–2.4 mmol/L
Lactate (arterial)	P: 0.6–1.8 mmol/L
LDH	P: 70–250 U/L
LH	P: 3–16 U/L
Magnesium	P: 0.75–1.05 mmol/L
Osmolality	P: 278–305 mosmol/kg
PTH	P: 0.8–8.5 pmol/L
Potassium	P: 3.5–5.3 mmol/L
Prolactin ♂	P: <450 U/L
Prolactin ♀	P: <600 U/L
PSA	P: 0–4 mcg/mL
Protein (total)	P: 60–80 g/L
Red cell folate	B: 0.36–1.44 μmol/L
Renin (erect)	P: 2.8–4.5 pmol/mL/h
Renin (recumbent)	P: 1.1–2.7 pmol/mL/h
Sodium	P: 135–145 mmol/L
TBG	P: 7–17 mg/L
TSH	P: 0.5–4.2 mU/L
T4	P: 70–140 nmol/L
Free T4	P: 9–22 pmol/L
TIBC	S: 54–75 μmol/L
Triglycerides	P: 0.50–2.3 mmol/L
T3	P: 1.2–3.0 nmol/L
Troponin T	P: <0.1 mcg/L
Urate ♂	P: 210–480 μmol/L
Urate ♀	P: 150–390 μmol/L
Urea	P: 2.5–6.7 mmol/L
Vitamin B12	S: 0.13–0.68 nmol/L
Vitamin D	S: 50 nmol/L

Arterial Blood Gases

pH	7.35–7.45
PaCO₂	4.7–6.0 kPa
PaO₂	>10.6 kPa
Base excess	±2 mmol/L

Urine

Cortisol (free)	<280 nmol/24h
Hydroxyindole acetic acid	16–73 μmol/24h
Hydroxymethylmandelic acid	16–48 μmol/24h
Metanephrines	0.03–0.69 μmol/mmol cr.
Osmolality	350–1000 mosmol/kg
17-Oxogenic steroids ♂	28–30 μmol/24h
17-Oxogenic steroids ♀	21–66 μmol/24h
17-Oxosteroids ♂	17–76 μmol/24h
17-Oxosteroids ♀	14–59 μmol/24h
Phosphate (inorganic)	15–50 mmol/24h
Potassium	14–120 mmol/24h
Protein	<150 mg/24h
Protein/creatinine ratio	<3 mg/mmol
Sodium	100–250 mmol/24h

Haematology

WCC	4.0–11.0 ×10⁹/L
RBC ♂	4.5–6.5 ×10¹²/L
RBC ♀	3.9–5.6 ×10¹²/L
Hb ♂	130–180 g/L
Hb ♀	115–160 g/L
PCV ♂	0.4–0.54 L/L
PCV ♀	0.37–0.47 L/L
MCV	76–96 fL
MCH	27–32 pg
MCHC	300–360 g/L
RDW	11.6–14.6%
Neutrophils	2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes	1.0–4.5 ×10⁹/L (20–45%)
Eosinophils	0.04–0.44 ×10⁹/L (1–6%)
Basophils	0–0.10 ×10⁹/L (0–1%)
Monocytes	0.2–0.8 ×10⁹/L (2–10%)
Platelets	150–400 ×10⁹/L
Reticulocytes	0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time	10–14 s
APTT	35–45 s

Paediatric

Pulse Rate (bpm)
Neonate	140–160
Infant <1yr	120–140
1–5 years	110–130
5–12 years	80–120
>12 years	70–100
Respiratory Rate (tachypnoea)
0–2 months	≥60/min
2–12 months	≥50/min
1–5 years	≥40/min
>5 years	≥30/min
Blood Pressure (mmHg)
Term	65/45
1 year	75/50
4 years	85/60
8 years	95/65
10 years	100/70
Weight Formulas
3–12 months	(a + 9)/2 kg
1–6 years	2a + 8 kg
>6 years	(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn	13–20
1 month	11–18
2 months	10–15
1–2 years	10–13
>2 years	11–14
MUAC (6 months–5 years)
Obese	>17.5 cm
Normal	13.5–17.4 cm
At risk	12.5–13.4 cm
Moderate malnutrition	11.5–12.4 cm
Severe malnutrition	<11.5 cm
Developmental Milestones
Social smile	1.5 months
Head control	4 months
Sits unsupported	7 months
Crawls	10 months
Stands unsupported	10–12 months
Walks	12–13 months
Talks	18 months
CSF WBC (/mm³)
Term newborn	0–25
>2 weeks	0–5

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