Synopsis
Recognise deficiency-related neuropathy, myelopathy, ataxia and encephalopathy, identify malabsorption and functional deficiency, and replace nutrients urgently without masking a second diagnosis or causing refeeding harm.
- Vitamin B12 deficiency can cause peripheral neuropathy, optic neuropathy, cognitive or psychiatric change and subacute combined degeneration, sometimes with a normal haemoglobin and mean cell volume.
- Posterior-column sensory loss plus corticospinal signs suggests B12 or copper-related myelopathy; a clear sensory level, sphincter dysfunction or rapid progression still requires urgent spinal imaging.
- Thiamine deficiency causes Wernicke encephalopathy, painful or weak neuropathy and cardiovascular beriberi; treat suspected neurological deficiency parenterally before or alongside carbohydrate when feasible rather than awaiting a blood concentration, without delaying emergency glucose.
- Vitamin E deficiency produces a spinocerebellar and large-fibre sensory syndrome with areflexia, dysarthria and sometimes retinopathy, especially after fat malabsorption or in inherited transport disease.
- Copper deficiency can mimic B12 disease after upper gastrointestinal surgery or excessive zinc exposure and may coexist with anaemia, neutropenia and peripheral neuropathy.
- Both pyridoxine deficiency and excessive long-term vitamin B6 supplementation can injure peripheral nerves, so supplement dose and duration belong in the exposure history.
- Nitrous oxide oxidises cobalamin and can cause functional B12 inactivation with myeloneuropathy even when a measured serum B12 concentration appears non-low.
- Severe malnutrition creates refeeding risk: replace urgent thiamine and correct electrolytes with a controlled nutrition plan rather than delivering unrestricted calories and fluid.
Key red flags
Confusion, eye-movement abnormality or acute ataxia in malnutrition or alcohol dependence requires immediate parenteral thiamine before or alongside planned glucose-containing nutrition, while urgent hypoglycaemia is corrected without delay.
A sensory level, new bladder dysfunction, rapidly progressive paraplegia or severe spinal pain needs emergency cord-compression or inflammatory imaging despite a low vitamin result.
Breathlessness, oedema, arrhythmia or circulatory failure during refeeding requires immediate electrolyte, cardiac and nutrition-team management.
Progressive visual loss with B12 or vitamin E deficiency requires urgent ophthalmic and neurological assessment because delayed axonal injury may be irreversible.
A patient continuing nitrous oxide exposure or high-dose pyridoxine while receiving replacement will continue to accumulate neurological injury.
Investigation priorities
Identify confirmed or indeterminate B12 status using the current NICE diagnostic thresholds and clinical context.
Management branches
Paraesthesia, sensory ataxia, myelopathy, optic or cognitive symptoms occur with confirmed or strongly suspected B12 deficiency.
- Take total or active B12, full blood count and cause-directed samples before treatment when this creates no harmful delay and document supplements and nitrous oxide.
- Start intramuscular hydroxocobalamin promptly for significant neurological disease using the BNF or local loading regimen and do not wait for macrocytosis.
- Investigate autoimmune gastritis, diet, coeliac or ileal disease, medicines and surgery and stop nitrous oxide exposure.
- Follow neurological response over months and provide lifelong maintenance when an irreversible malabsorption cause requires it.