Genetics
Genetic diseases of thiamine transport are rare but serious. Thiamine responsive megaloblastic anemia syndrome (TRMA) with diabetes mellitus and sensorineural deafness is an autosomal recessive disorder caused by mutations in the gene SLC19A2, a high affinity thiamine transporter. TRMA patients do not show signs of systemic thiamine deficiency, suggesting redundancy in the thiamine transport system. This has led to the discovery of a second high-affinity thiamine transporter, SLC19A3. Leigh disease (subacute necrotising encephalomyelopathy) is an inherited disorder that affects mostly infants in the first years of life and is invariably fatal. Pathological similarities between Leigh disease and WE led to the hypothesis that the cause was a defect in thiamine metabolism. One of the most consistent findings has been an abnormality of the activation of the pyruvate dehydrogenase complex.Mutations in the SLC19A3 gene have been linked to biotin-thiamine responsive basal ganglia disease, which is treated with pharmacological doses of thiamine and biotin, another B vitamin. Other disorders in which a putative role for thiamine has been implicated include subacute necrotising encephalomyelopathy, opsoclonus myoclonus syndrome (a paraneoplastic syndrome), and Nigerian seasonal ataxia (or African seasonal ataxia). In addition, several inherited disorders of ThDP-dependent enzymes have been reported, which may respond to thiamine treatment. Pathophysiology
Thiamine in the human body has a half-life of 18 days and is quickly exhausted, particularly when metabolic demands exceed intake. A derivative of thiamine, thiamine pyrophosphate (TPP), is a cofactor involved in the citric acid cycle, as well as connecting the breakdown of sugars with the citric acid cycle.
Ethanol per se inhibits thiamine transport in the gastrointestinal system and blocks phosphorylation of thiamine to its cofactor form (ThDP).Following improved nutrition and the removal of alcohol consumption, some impairments linked with thiamine deficiency are reversed, in particular poor brain functionality, although in more severe cases, Wernicke–Korsakoff syndrome leaves permanent damage. (See delirium tremens.) Wet beriberi
Wet beriberi affects the heart and circulatory system. It is sometimes fatal, as it causes a combination of heart failure and weakening of the capillary walls, which causes the peripheral tissues to become edematous. Wet beriberi is characterized by:

Increased heart rate
Vasodilation leading to decreased systemic vascular resistance, and high-output heart failure
Elevated jugular venous pressure
Dyspnea (shortness of breath) on exertion
Paroxysmal nocturnal dyspnea
Peripheral edema (swelling of lower legs) or generalized edema (swelling throughout the body)
Dilated cardiomyopathy

Gastrointestinal beriberi
Gastrointestinal beriberi causes abdominal pain. It is characterized by:

Abdominal pain
Nausea
Vomiting
Lactic acidosis

Infants
Infantile beriberi usually occurs between two and six months of age in children whose mothers have inadequate thiamine intake. It may present as either wet or dry beriberi.In the acute form, the baby develops dyspnea and cyanosis and soon dies of heart failure.