Most dietary deficiency of thiamine worldwide is the result of poor dietary intake. In western countries, the primary causes of thiamine deficiency are alcoholism and chronic illness, such as cancer. Alcohol is known to interfere directly with the absorption of thiamine and with the synthesis of thiamine pyrophosphate. Malnourished individuals with alcoholic liver disease are also at increased risk of thiamine deficiency because of diminished storage sites in liver and muscle. Thiamine should always be replenished when refeeding a patient with alcoholism, as carbohydrate repletion without adequate thiamine can precipitate acute thiamine deficiency.
Thiamine deficiency in its early stage induces anorexia, irritability, apathy, and generalized weakness. Prolonged thiamine deficiency causes beriberi, which is classically categorized as wet or dry, although there is considerable overlap. In either form of beriberi, patients may complain of pain and parathesia. Wet beriberi presents primarily with cardiovascular symptoms, due to impaired myocardial energy metabolism and dysautonomia, and can occur after 3 months of a thiamine-deficient diet. Patients present with an enlarged heart, tachycardia, high-output congestive heart failure, peripheral edema, and peripheral neuritis. Patients with dry beriberi present with a symmetric peripheral neuropathy of the motor and sensory systems with diminished reflexes. The neuropathy affects the legs most markedly, and patients have difficulty rising from a squatting position.
Alcoholic patients with chronic thiamine deficiency may also have central nervous system manifestations known as Wernicke's encephalopathy, consisting of horizontal nystagmus, ophthalmoplegia (due to weakness of one or more extraocular muscles), cerebellar ataxia, and mental impairment. When there is an additional loss of memory and a confabulatory psychosis, the syndrome is known as Wernicke-Korsakoff syndrome. Although this syndrome is generally described in alcoholic patients, there may be a genetic predisposition to Wernicke-Korsakoff that involves a variant transketolase isozyme.
In severely malnourished infants 2 to 3 months old, thiamine deficiency may occur precipitously with sudden cardiovascular failure and collapse, resulting in death within hours. In addition, infants with thiamine deficiency may present with features suggesting meningitis, including vomiting, nystagmus, and convulsions. An aphonic presentation has also been described in which there is extreme irritability and either a very hoarse cry or total inability to emit any noise whatsoever (a silent scream).
The laboratory diagnosis of thiamine deficiency is usually made by a functional enzymatic assay of transketolase activity measured before and after the addition of thiamine pyrophosphate. A >25% stimulation by the addition of thiamine pyrophosphate (an activity coefficient of 1.25) is taken as abnormal. Thiamine or the phosphorylated esters of thiamine in serum or blood can also be measured by high-performance liquid chromatography (HPLC) to detect deficiency. Moreover, a urinary level of thiamine <27 ug per gram of creatinine per day is abnormal. In measuring urinary excretion of thiamine, one should make sure the patient is not taking diuretics, which increase thiamine excretion.