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This, in turn, has led to delayed diagnosis, notably in people presenting solely with neurological symptoms.68232425 However, in many people, neurological and neuropsychological or cognitive symptoms (box 1, fig 1) are the main presenting symptoms.23 Anaemia is present in fewer than 20% of people with B 12 deficiency.26 Cobalamin analogue formation maybe related to more prominent neurological manifestations.30 Frequently reported signs and symptoms of B 12 deficiency92326272829 Brain function: Brain fog, memory problems, cognitive impairment, insomnia, headaches (especially migraine), behavioural changes, learning problems, nominal aphasia Mood: Mood swings, irritability, depression, anxiety, hallucinations, delusions, psychosis Sensory: Peripheral paraesthesia (pins and needles), numbness, neuropathic pains, poor balance, reduced vibration sense or proprioception (joint position sense), tinnitus, ataxia, taste impairment, sometimes myelopathy Constitutional: Fatigue, anaemia (either macrocytic, or normocytic when also iron deficient or associated with thalassaemia minor), other cytopenia, abdominal complaints, malabsorption, failure to thrive, weight loss, diarrhoea, hyperpigmentation, glossitis, (aphthous) stomatitis, infertility, urinary tract infections Motor: Muscle weakness, altered reflexes (increased in degeneration of the spinal cord, reduced when peripheral neuropathy dominates), spasticity, seizures, cardiomyopathy Autonomic: Urinary and/or faecal incontinence, postural hypotension or dizziness, erectile dysfunction Diagnosing B 12 deficiency can be challenging because no single specific measurement exists to reliably diagnose or refute the presence of B 12 deficiency11122627 (box 2)

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Therefore, we assessed 39 mainly functional polymorphisms in genes involved in inflammation, in particular the NFB pathway, in a cohort of 738 Danish IBD patients previously naive to anti-TNF therapy