Thiamine deficiency


Thiamine deficiency is a medical condition of low levels of thiamine. A severe and chronic form is known as beriberi. The name beriberi was possibly borrowed in the 18th century from the Sinhalese phrase බැරි බැරි, owing to the weakness caused by the condition. The two main types in adults are wet beriberi and dry beriberi. Wet beriberi affects the cardiovascular system, resulting in a fast heart rate, shortness of breath, and leg swelling. Dry beriberi affects the nervous system, resulting in numbness of the hands and feet, confusion, trouble moving the legs, and pain. A form with loss of appetite and constipation may also occur. Another type, acute beriberi, found mostly in babies, presents with loss of appetite, vomiting, lactic acidosis, changes in heart rate, and enlargement of the heart.
Risk factors include a diet of mostly white rice, alcoholism, dialysis, chronic diarrhea, and taking high doses of diuretics. In rare cases, it may be due to a genetic condition that results in difficulties absorbing thiamine found in food. Wernicke encephalopathy and Korsakoff syndrome are forms of dry beriberi. Diagnosis is based on symptoms, low levels of thiamine in the urine, high blood lactate, and improvement with thiamine supplementation.
Treatment is by thiamine supplementation, either by mouth or by injection. With treatment, symptoms generally resolve in a few weeks. The disease may be prevented at the population level through the fortification of food.
Thiamine deficiency is rare in most of the developed world. It remains relatively common in sub-Saharan Africa. Outbreaks have been seen in refugee camps. Thiamine deficiency has been described for thousands of years in Asia, and became more common in the late 1800s with the increased processing of rice.

Signs and symptoms

Symptoms of beriberi include weight loss, emotional disturbances, impaired sensory perception, weakness and pain in the limbs, and periods of irregular heart rate. Edema is common. It may increase the amount of lactic acid and pyruvic acid within the blood. In advanced cases, the disease may cause high-output cardiac failure and death.
Symptoms may occur concurrently with those of Wernicke's encephalopathy, a primarily neurological thiamine deficiency-related condition.
Beriberi is divided into four categories. The first three are historical and the fourth, gastrointestinal beriberi, was recognized in 2004:
  • Dry beriberi especially affects the peripheral nervous system.
  • Wet beriberi especially affects the cardiovascular system and other bodily systems.
  • Infantile beriberi affects the babies of malnourished mothers.
  • Gastrointestinal beriberi affects the digestive system and other bodily systems.

    Dry beriberi

Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves. It is also referred to as endemic neuritis. It is characterized by:
  • Difficulty with walking
  • Tingling or loss of sensation in hands and feet
  • Loss of tendon reflexes
  • Loss of muscle function or paralysis of the lower legs
  • Mental confusion/speech difficulties
  • Pain
  • Involuntary eye movements
  • Vomiting
A selective impairment of the large proprioceptive sensory fibers without motor impairment can occur and present as a prominent sensory ataxia, which is a loss of balance and coordination due to loss of the proprioceptive inputs from the periphery and loss of position sense.

Brain disease

, Korsakoff syndrome, and Wernicke–Korsakoff syndrome are forms of dry beriberi.
Wernicke's encephalopathy is the most frequently encountered manifestation of thiamine deficiency in Western society, though it may also occur in patients with impaired nutrition from other causes, such as gastrointestinal disease, those with HIV/AIDS, and with the injudicious administration of parenteral glucose or hyperalimentation without adequate B-vitamin supplementation. This is a striking neuro-psychiatric disorder characterized by paralysis of eye movements, abnormal stance and gait, and markedly deranged mental function.
Korsakoff syndrome, in general, is considered to occur with deterioration of brain function in patients initially diagnosed with WE. This is an amnestic-confabulatory syndrome characterized by retrograde and anterograde amnesia, impairment of conceptual functions, and decreased spontaneity and initiative.
Alcoholics may have thiamine deficiency because of:
  • Inadequate nutritional intake: Alcoholics tend to intake less than the recommended amount of thiamine.
  • Decreased uptake of thiamine from the GI tract: Active transport of thiamine into enterocytes is disturbed during acute alcohol exposure.
  • Liver thiamine stores are reduced due to hepatic steatosis or fibrosis.
  • Impaired thiamine utilization: Magnesium, which is required for the binding of thiamine to thiamine-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient use of any thiamine that does reach the cells will further exacerbate the thiamine deficiency.
  • Ethanol per se inhibits thiamine transport in the gastrointestinal system and blocks phosphorylation of thiamine to its cofactor form.
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.

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:
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. These symptoms may be described in infantile beriberi:
  • Hoarseness, where the child makes moves to moan, but emits no sound or just faint moans caused by nerve paralysis
  • Weight loss, becoming thinner and then marasmic as the disease progresses
  • Vomiting
  • Diarrhea
  • Pale skin
  • Edema
  • Ill temper
  • Alterations of the cardiovascular system, especially tachycardia
  • Convulsions occasionally observed in the terminal stages

    Cause

Beriberi is often caused by eating a diet with a very high proportion of calorie rich polished rice or cassava root, without much if any thiamine-containing animal products or vegetables.
It may also be caused by shortcomings other than inadequate intake – diseases or operations on the digestive tract, alcoholism, dialysis or genetic deficiencies. All those causes mainly affect the central nervous system, and provoke the development of Wernicke's encephalopathy.
Wernicke's disease is one of the most prevalent neurological or neuropsychiatric diseases. In autopsy series, features of Wernicke lesions are observed in approximately 2% of general cases. Medical record research shows that about 85% had not been diagnosed, although only 19% would be asymptomatic. In children, only 58% were diagnosed. In alcohol abusers, autopsy series showed neurological damages at rates of 12.5% or more. Mortality caused by Wernicke's disease reaches 17% of diseases, which means 3.4/1000 or about 25 million contemporaries. The number of people with Wernicke's disease may be even higher, considering that early stages may have dysfunctions prior to the production of observable lesions at necropsy. In addition, uncounted numbers of people can experience fetal damage and subsequent diseases.

Genetics

Genetic diseases of thiamine transport are rare but serious. Thiamine responsive megaloblastic anemia syndrome 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 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, and Nigerian 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 17 days and is quickly exhausted, particularly when metabolic demands exceed intake. A derivative of thiamine, thiamine pyrophosphate, is a cofactor involved in the citric acid cycle, as well as connecting the breakdown of sugars with the citric acid cycle. The citric acid cycle is a central metabolic pathway involved in the regulation of carbohydrate, lipid, and amino acid metabolism, and its disruption due to thiamine deficiency inhibits the production of many molecules including the neurotransmitters glutamic acid and GABA. Additionally, thiamine may also be directly involved in neuromodulation.