History and exam
Key diagnostic factors
common
presence of risk factors
Key risk factors include chronic alcohol excess, malnutrition, a staple diet of polished rice, age <1 year in endemic thiamine deficient region, refeeding syndrome, hyperemesis gravidarum, recurrent vomiting/chronic diarrhoea, gastrointestinal surgery, and renal replacement therapy.
ocular abnormalities (Wernicke's encephalopathy)
Acute, severe deficiency may lead to Wernicke's encephalopathy, which is characterised by the classic triad of altered mental status (e.g., acute confusion), ataxia, and ocular abnormalities (e.g., nystagmus and strabismus).
confusion (Wernicke's encephalopathy)
Acute, severe deficiency may lead to Wernicke's encephalopathy, which is characterised by the classic triad of altered mental status (e.g., acute confusion), ataxia, and ocular abnormalities (e.g., nystagmus and strabismus).
ataxia (Wernicke's encephalopathy)
Acute, severe deficiency may lead to Wernicke's encephalopathy, which is characterised by the classic triad of altered mental status (e.g., acute confusion), ataxia, and ocular abnormalities (e.g., nystagmus and strabismus).
Other diagnostic factors
common
fatigue
The early, subclinical stages of vitamin B1 deficiency present with non-specific symptoms, such as fatigue and muscle aches.[41]
muscle aches
The early, subclinical stages of vitamin B1 deficiency present with non-specific symptoms, such as fatigue and muscle aches.
incessant crying (infantile beriberi)
Initially a loud, hoarse cry, which evolves into a “silent cry,” or aphonia.
anorexia (infantile beriberi)
Refusal to breastfeed or loss of appetite.
bulging fontanelle (infantile beriberi)
In areas with low awareness of thiamine deficiency, symptoms are easily mistaken for meningitis.[10]
dyspnoea and orthopnoea (wet beriberi)
Symptoms of cardiac failure.
tachycardia (wet beriberi)
Sign of cardiac failure.
peripheral cyanosis (Shoshin beriberi)
Sign of cardiac failure with peripheral vasoconstriction.
peripheral or dependent oedema (wet beriberi)
Sign of cardiac failure.
decreased sensation (dry beriberi)
Dry beriberi is characterised by a symmetrical distal peripheral polyneuropathy (particularly of the legs) with sensory and motor impairments.[7]
Can present with paraesthesia, reduced knee jerks and other tendon reflexes, and progressive severe weakness with muscle wasting.
reduced tendon reflexes (dry beriberi)
Dry beriberi is characterised by a symmetrical distal peripheral polyneuropathy (particularly of the legs) with sensory and motor impairments.[7]
Can present with paraesthesia, reduced knee jerks and other tendon reflexes, and progressive severe weakness with muscle wasting.
muscle weakness and wasting (dry beriberi)
Dry beriberi is characterised by a symmetrical distal peripheral polyneuropathy (particularly of the legs) with sensory and motor impairments.[7]
Can present with paraesthesia, reduced knee jerks and other tendon reflexes, and progressive severe weakness with muscle wasting.
abdominal pain (gastrointestinal beriberi)
Gastrointestinal beriberi can present with severe abdominal pain and minimal clinical findings on examination.
Risk factors
strong
chronic alcohol excess
In the developed world, vitamin B1 deficiency presenting as Wernicke's encephalopathy occurs mainly in people with alcohol misuse disorders, particularly in the context of poor nutritional intake.[3]
Alcohol may block the active-transport mechanism for the absorption of thiamine in the gastrointestinal tract.[3][14][15]
malnutrition
Vitamin B1 deficiency may result from poor nutritional intake.
Dietary intake of about 1 mg of thiamine per day, obtainable from foods including whole-grain cereals, pulses, nuts, and meat, prevents clinical deficiency.[1][40][41]
Those at risk of malnutrition-associated deficiency include people with alcohol use disorders and people who follow extreme weight-loss diets for long periods of time without supplementation.[46]
staple diet of polished rice
age <1 year in endemic thiamine-deficient region
refeeding syndrome
Thiamine is a co-factor in the metabolism of carbohydrates. Therefore, vitamin B1 deficiency should be considered and treated before refeeding orally, enterally, or parenterally (including simple intravenous glucose).[19][20]
Inadequate or absent thiamine supplementation in total parenteral nutrition can lead to vitamin B1 deficiency.[17]
hyperemesis gravidarum
In women with hyperemesis gravidarum, the thiamine absorption rate is decreased significantly due to excessive vomiting and poor oral intake, with resulting symptomatic thiamine deficiency.[34]
There is an increased demand for thiamine during pregnancy from the fetus and the hypermetabolic state of pregnancy itself.[9]
Evidence from case reports suggests that women with hyperemesis gravidarum are at risk of vitamin B1 deficiency, which may lead to Wernicke’s encephalopathy if untreated, especially during refeeding.[34][35]
Nausea, vomiting, and a loss of appetite are common, non-specific presenting symptoms of thiamine deficiency and overlap with symptoms of hyperemesis gravidarum such that early diagnosis is often missed.[34]
recurrent vomiting/chronic diarrhoea
gastrointestinal surgery
Gastrointestinal surgery, including bariatric surgery, may lead to vitamin B1 deficiency.[22][23][24][25]
Deficiency can result from a decrease in the mucosal absorptive surface of the ileum following surgery, sustained postoperative vomiting, or poor oral intake.[7][26]
Vitamin B1 deficiency has been reported in 16% to 29% of patients planning to undergo bariatric surgery for obesity.[16]
weak
obesity
Increased caloric intake leads to an increased load on metabolic pathways - in particular, glucose metabolism - and an increased demand for micronutrients such as thiamine as enzyme co-factors.[16]
Vitamin B1 deficiency has been reported in 16% to 29% of patients planning to undergo bariatric surgery for obesity.[16]
magnesium deficiency
Magnesium is a co-factor for thiamine-containing enzymes.[16] Thus, an adequate supply of magnesium is required in order for thiamine to function fully.
Causes of magnesium deficiency include increased loss of magnesium (e.g., diarrhoea following bariatric surgery), low dietary intake (e.g., in alcohol-related liver disease), increased urinary loss of magnesium in distal tubular dysfunction, and drugs (e.g., proton-pump inhibitors).[16][37][38]
HIV infection/AIDS
HIV infection and AIDS has been associated with increased risk of vitamin B1 deficiency.[36]
cancer and chemotherapy
The anorexia, nausea and vomiting, malabsorption, and accelerated metabolism of thiamine associated with malignancy places these patients at increased risk of vitamin B1 deficiency.[30][31]
Gastrointestinal malignancies and haematological malignancies are particularly implicated.[30] Some chemotherapeutic agents interfere with thiamine function.[30]
thiaminase- and thiamine antagonist-containing diet
Thiaminases break down thiamine in food, and thiamine antagonists can interfere with the absorption of thiamine. Certain foods that contain thiaminases (e.g., fermented fish, shellfish) or thiamine antagonists (e.g., tea, coffee, betel nuts, red cabbage) can result in vitamin B1 deficiency.[18]
genetic mutation
Several rare syndromes of thiamine metabolism dysfunction have been described. These syndromes result from genetic defects in thiamine transport and metabolism and are generally detected in younger individuals.[27][28]
Thiamine-responsive megaloblastic anaemia (TRMA) syndrome is a rare disease characterised by thiamine-responsive anaemia, diabetes, and deafness; it is caused by recessively inherited mutations in the SLC19A2 gene.[28][29] Mutations in SLC19A3, TPK1, and SLC25A19 genes predominantly result in neurological sequelae with episodic encephalopathy, often triggered by febrile illness or infection.[27][28]
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