Approach

Vitamin B1 deficiency is a clinical diagnosis and can present in several ways depending on the presence of comorbidities, age, and general susceptibility. As the presenting symptoms are nonspecific, 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.

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

Clinical features

Subclinical deficiency

  • The early stages of vitamin B1 deficiency present with nonspecific symptoms, such as fatigue and muscle aches.

Wernicke encephalopathy

  • Acute, severe deficiency may lead to Wernicke encephalopathy, which is characterized by the classic triad of mental state changes (e.g., acute confusion), ataxia, and ocular abnormalities (e.g., nystagmus and strabismus).[45][46] One study of autopsied patients found that, in patients who had neuropathologic features of Wernicke encephalopathy, retrospective review of case notes showed that this classic triad of symptoms is absent in up to 90% of cases, while 19% of patients had no clinical features.[47] Wernicke encephalopathy is the most common form of thiamine deficiency in adults and older children.[1]

Wet beriberi

  • Cardiac sequelae in wet beriberi can occur with acute or chronic deficiency. These can either be high-output cardiac failure with peripheral vasodilation, peripheral edema, dyspnea, and orthopnea, or, less frequently, low-output cardiac failure with lactic acidosis and peripheral cyanosis (also known as Shoshin beriberi). However, cardiac failure from thiamine deficiency is rare in developed settings, so neither screening for thiamine deficiency, nor routine thiamine supplementation, are justified for people with heart failure unless other clinical signs of beriberi are present.[48]

Dry beriberi

  • Presents as a distal peripheral polyneuropathy (particularly of the legs) following chronic vitamin B1 deficiency. It is characterized by paresthesia, reduced knee jerks and other tendon reflexes, and progressive severe weakness with muscle wasting.

Infantile beriberi

  • Mostly occurs in infants exclusively breastfed by vitamin B1-deficient mothers, and exists in 3 forms; cardiogenic (cardiac failure and cyanosis), aphonic (vocal-cord paralysis), and pseudomeningitic (clinical meningismus with negative CSF findings).[1]

  • In younger infants (<4 months), early signs are nonspecific, including irritability, refusal to breastfeed, tachycardia and tachypnea, vomiting, and incessant crying.[1] As the disease progresses further signs and symptoms of congestive heart failure begin to appear, such as shortness of breath, hepatomegaly, and cyanosis.[1] Older infants may present with predominant neurological symptoms, including loss of appetite, nystagmus, bulging fontanelle, and loss of consciousness.[1]

Risk factors

Thiamine deficiency disorders are more prevalent in regions where diets are monotonous (e.g., diet based around polished rice, which is deficient in thiamine) and conditions lead to inadequate food intake (e.g., drought, famine, conflict, displacement), especially in individuals with an increased metabolic need (e.g., pregnancy, infancy, critical illness).[1][4]

In the developed world, vitamin B1 (thiamine) deficiency presenting as Wernicke encephalopathy occurs mainly in those who chronically abuse alcohol, particularly in the context of poor nutritional intake.[2]

Non-alcoholic causes of vitamin B1 deficiency can be due to inadequate intake (e.g., fasting, starvation, malnutrition, the use of unbalanced diets), malabsorptive conditions (e.g., gastrointestinal surgery, conditions that cause recurrent vomiting and/or diarrhea), and conditions with increased demand (e.g., cancer, thyrotoxicosis, infection).[7][8]

Inadequate thiamine supplementation in total parenteral nutrition can lead to vitamin B1 deficiency.[28] Gastrointestinal surgery (e.g., gastric bypass) may reduce the area of intestinal and gastric mucosa available for absorbing thiamine, and may cause recurrent postoperative vomiting and poor appetite, resulting in malnutrition.[11]

Magnesium deficiency (common in those who chronically abuse alcohol) and conditions associated with recurrent vomiting or chronic diarrhea predispose to the development of vitamin B1 deficiency.

Other conditions associated with vitamin B1 deficiency are cancer (particularly gastrointestinal and hematologic malignancies) and chemotherapy treatment, and HIV infection/AIDS.

Diets rich in certain foods, such as fermented fish (source of thiaminase), betel nuts, tea, coffee, and red cabbage (sources of thiamine antagonists), can result in vitamin B1 deficiency.[30][31]

Confirmation of vitamin B1 deficiency

Before starting thiamine-replacement therapy, a blood sample should be taken for erythrocyte thiamine pyrophosphate. Erythrocyte thiamine pyrophosphate is a good indicator of the body stores of thiamine, as thiamine depletes at the same rate in erythrocytes as in other tissues.[49] As this test will take several days, treatment should not be delayed while awaiting the result. The result can be used to retrospectively confirm thiamine deficiency.

It should be noted that red cell transketolase is no longer used as a measure of thiamine deficiency as it is very unstable, and therefore the results are unreliable and difficult to reproduce.

Further investigations

Lactate is elevated in any condition causing an increase in anaerobic respiration and should be measured in response to an unexplained raised anion gap metabolic acidosis found on arterial blood gas measurement. While vitamin B1 deficiency is associated with lactic acidosis and an elevated lactate, their presence is not diagnostic and their absence does not exclude the deficiency.

All patients presenting in high-output cardiac failure should have thyroid function tests urgently checked to rule out thyrotoxicosis. Thyrotoxicosis is represented by a high free T4/T3 and a suppressed TSH.

MRI of the brain can detect changes associated with Wernicke encephalopathy, but these are not entirely specific to the condition. Wernicke encephalopathy results in bilateral increased T2 signal in the paraventricular regions of the thalamus, hypothalamus, mammillary bodies, periaqueductal region, fourth ventricle floor, and midline cerebellum.[50] With a sensitivity of 53% and a specificity of 93% for Wernicke encephalopathy, this investigation is most useful to rule out the diagnosis.[51]

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