Approach

Vitamin B1 deficiency is a clinical diagnosis and can present in several ways depending on the cause of deficiency, presence of comorbidities, age, and general susceptibility.[7]

Patient history may include excessive alcohol consumption and poor nutritional status. Enquire about the patient’s medical history (e.g., bariatric surgery, chemotherapy). Drug history should be reviewed; diuretic therapy (e.g., furosemide) has been associated with vitamin B1 deficiency.[49][50][51]

As the presenting symptoms are non-specific, it is important to ascertain whether the patient has any risk factors for vitamin B1 deficiency. There should be a low threshold for the initiation of treatment.[1][55]

Patients at risk of vitamin B1 deficiency and those presenting with signs and symptoms of Wernicke's encephalopathy, wet beriberi, or dry beriberi should be treated with thiamine replacement therapy immediately and the response to treatment recorded while investigations to exclude other diagnoses are ongoing.[44]​ Clinical improvement with thiamine replacement therapy suggests a diagnosis of vitamin B1 deficiency.[7]

Clinical features

Patient signs and symptoms may suggest the following.

Subclinical deficiency

Early stages of vitamin B1 deficiency present with non-specific symptoms, such as fatigue and muscle aches.[41]

Wernicke's encephalopathy

Characterised by the classic triad of altered mental status, ataxia, and ocular abnormalities (e.g., nystagmus and strabismus), although vague presenting features may also be seen.[56][57]​​​ The classic triad of symptoms was present in 39% of patients in one retrospective cohort study of patients in Spain.[57]​ Wernicke’s encephalopathy is the most common form of thiamine deficiency in adults and older children.[10]

Wet beriberi

Cardiac sequelae in wet beriberi can occur with acute or chronic deficiency. These can manifest as high-output cardiac failure with peripheral vasodilation, dependent oedema, dyspnoea, and orthopnoea. Shoshnin beriberi occurs less frequently, and is characterised by low-output cardiac failure with lactic acidosis (due to hypoperfusion).[7]​​

Dry beriberi

Presents as a symmetrical distal peripheral polyneuropathy (particularly of the legs).[7]​ Characterised by paraesthesia, reduced knee jerks and other tendon reflexes, and progressive severe weakness with muscle wasting.

Gastrointestinal (GI) beriberi

Presents with abdominal pain and minimal clinical findings on examination.

Infantile beriberi

Mostly occurs in infants exclusively breastfed by vitamin B1-deficient mothers, and exists in three forms: cardiogenic (cardiac failure and cyanosis), aphonic (vocal-cord paralysis), and pseudo-meningitic (clinical meningismus with negative cerebrospinal fluid [CSF] findings).[10]

In younger infants (<4 months), early signs are non-specific, including irritability, refusal to breastfeed, tachycardia and tachypnoea, vomiting, and incessant crying.[10] As the disease progresses, signs and symptoms of congestive heart failure begin to appear (e.g., shortness of breath, hepatomegaly, and cyanosis).[10] Pulmonary hypertension has also been reported.[58][59]

Older infants may present with predominant neurological symptoms, including loss of appetite, nystagmus, bulging fontanelle, and loss of consciousness.[10]

Consider thiamine metabolism dysfunction syndrome when clinical presentation cannot otherwise be explained.

Thiamine metabolism dysfunction syndrome (THMD) comprises rare genetic disorders that impact vitamin B1 metabolism. Thiamine-responsive megaloblastic anaemia (TRMA) syndrome is 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]

Confirmation of vitamin B1 deficiency

Guidelines recommend measurement of thiamine pyrophosphate levels in whole blood or erythrocytes.[1][13]​​​ As this test takes several days, treatment should not be delayed while awaiting the result. The result can be used to retrospectively confirm thiamine deficiency.

Laboratory confirmation of thiamine deficiency is rarely performed in clinical practice due to cost and delay in obtaining results.​[7][44][54]​​ Response to a trial of thiamine supplementation is often used to confirm deficiency.[1]

Further investigations

While vitamin B1 deficiency is associated with lactic acidosis and a raised lactate, their presence is not diagnostic and their absence does not exclude the deficiency.[44]​ Depending on the context, it may be appropriate to investigate other possible causes of metabolic acidosis (e.g., salicylate toxicity, diabetic ketoacidosis, uraemia).

All patients presenting in high-output cardiac failure should have urgent thyroid function tests to rule out thyrotoxicosis.[60]​ Thyrotoxicosis is represented by raised free thyroxine (T4)/triiodothyronine (T3) and suppressed thyroid-stimulating hormone (TSH). It may be appropriate to investigate other possible causes of high-output cardiac failure, depending on the presentation.[60]​​

Magnetic resonance imaging (MRI) of the brain is useful to support a diagnosis of Wernicke's encephalopathy.[13][61]​​ In Wernicke’s encephalopathy, sensitivity is 53% and specificity is 93%.[13][62]​​ MRI changes in Wernicke's encephalopathy are often described as bilateral and symmetrical lesions in the thalamus, mammillary bodies, tectal plate, and periaqueductal region on T2-weighted imaging or fluid-attenuated inversion recovery (FLAIR) sequence.[13][61]​​

Echocardiography may be useful for diagnosis of wet beriberi and to help guide management.[7]

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