Vitamin B1: Thiamine Deficiency And Dependency

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Thiamine Deficiency And Dependency

 

The coenzyme thiamine pyrophosphate, the active form of thiamine

(vitamin B1), participates in carbohydrate metabolism through

decarboxylation of alpha-keto acids. Thiamine also acts as coenzyme to

the apoenzyme transketolase in the pentose monophosphate pathway for

glucose. Deficiency causes beriberi with peripheral neurologic,

cerebral, cardiovascular, and GI manifestations.

Etiology

 

Primary thiamine deficiency is caused by inadequate intake of

thiamine, particularly in people subsisting on highly polished rice.

Milling removes the husk, which contains most of the thiamine, but

boiling before husking disperses the vitamin throughout the grain,

thus preventing its loss.

 

Secondary thiamine deficiency is caused by increased requirement, as

in hyperthyroidism, pregnancy, lactation, and fever; impaired

absorption, as in prolonged diarrheas; and impaired utilization, as in

severe liver disease. A combination of decreased intake, impaired

absorption and utilization, increased requirements, and possibly an

apoenzyme defect occurs in alcoholism. Frequent, long-term, or highly

concentrated dextrose infusions, coupled with low thiamine intake, may

precipitate thiamine deficiency.

Pathology

 

The most advanced neural changes occur in the peripheral nerves,

particularly of the legs. The distal segments are characteristically

affected earliest and most severely. Degeneration of the medullary

sheath can occur in all tracts of the spinal cord, especially in the

posterior columns and in the anterior and posterior nerve roots.

Changes also occur in the anterior horn and posterior ganglion cells.

Lesions of hemorrhagic polioencephalitis occur in the brain when

deficiency is severe.

 

The heart is dilated and enlarged; muscle fibers are swollen,

fragmented, and vacuolized, with interstitial spaces dilated by fluid.

Vasodilation occurs and can result in some edema before frank

high-output heart failure occurs.

Symptoms and Signs

 

Early deficiency produces fatigue, irritation, poor memory, sleep

disturbances, precordial pain, anorexia, abdominal discomfort, and

constipation.

 

The syndrome of peripheral neurologic changes due to thiamine

deficiency is called dry beriberi. These changes are bilateral and

symmetric, involving predominantly the lower extremities, and begin

with paresthesias of the toes, burning of the feet (particularly

severe at night), muscle cramps in the calves, and pains in the legs.

Calf muscle tenderness, difficulty in rising from a squatting

position, a decrease in the vibratory sensation in the toes, and

plantar dysesthesia are early signs. A diagnosis of mild peripheral

neuropathy can be made when ankle jerks are absent. Continued

deficiency causes loss of knee jerk, loss of vibratory and position

sensation in the toes, atrophy of the calf and thigh muscles, and

finally footdrop and toedrop. The arms may be affected after leg signs

are well established.

 

Cerebral beriberi (Wernicke-Korsakoff syndrome) results from severe

acute deficiency superimposed on chronic deficiency (see Amnesias in

Ch. 169). Mental confusion, aphonia, and confabulation constitute the

early stage, called Korsakoff's syndrome. Cerebral blood flow is

markedly reduced and vascular resistance increased. Wernicke's

encephalopathy consists of nystagmus, total ophthalmoplegia, coma,

and, if untreated, death.

 

Cardiovascular (wet) beriberi (Shoshin beriberi) occurs in thiamine

deficiency when myocardial disease is prominent. This causes a high

cardiac output with vasodilation and warm extremities. Before heart

failure occurs, tachycardia, a wide pulse pressure, sweating, warm

skin, and lactic acidosis develop. With heart failure, orthopnea and

pulmonary and peripheral edema occur; vasodilation continues,

sometimes resulting in shock.

 

Infantile beriberi occurs in infants (usually between the 2nd and 4th

mo of life) who are breastfed by thiamine-deficient mothers. Heart

failure, aphonia, and absent deep tendon reflexes are characteristic.

Laboratory Findings

 

Elevated blood pyruvate and lactate and diminished urinary thiamine

excretion (< 50 µg/day) are consistent with the diagnosis of beriberi.

Erythrocyte transketolase activity diminishes before and increases

after administration of thiamine pyrophosphate (TPP effect) and is a

sensitive indicator of tissue stores. Variations in apoenzyme levels

in some cases may complicate interpretation of the test.

Diagnosis

 

A form of polyneuropathy, which does not respond to thiamine, occurs

in uncontrolled or long-standing diabetes mellitus and in alcoholism

and is clinically similar to that of thiamine deficiency. Other forms

of bilateral symmetric polyneuropathy beginning in the legs are

uncommon. Single-nerve neuritides (mononeuropathies), such as

sciatica, and polyneuropathies beginning elsewhere in the body are

unlikely to be due to thiamine deficiency.

 

Diagnosis of cardiovascular beriberi is difficult when thiamine

deficiency is complicated by hypertensive or degenerative heart

disease, viral myocardiopathy, or rheumatic fever. A therapeutic trial

of thiamine can be helpful in making the diagnosis.

Treatment

 

For mild polyneuropathy, 10 to 20 mg/day of thiamine is given in

divided doses for 2 wk, followed by a nutritious diet. The dosage is

20 to 30 mg/day for moderate or advanced neuropathy and should be

continued for several weeks after the symptoms disappear. The edema

and congestion of Shoshin beriberi respond in a few hours to 100

mg/day of thiamine IV, which should be continued for several days,

plus bed rest. Heart failure due to beriberi responds poorly to

digitalis or diuretics.

 

For Wernicke-Korsakoff syndrome, thiamine 50 to 100 mg IM or IV bid

must usually be given for several days, followed by 10 to 20 mg daily

until a therapeutic response is obtained. Anaphylactic reactions to IV

thiamine unrelated to the dose are rare.

 

Thiamine deficiency is often associated with other B-complex

deficiencies, and multiple water-soluble vitamin therapy at 5 to 10

times the RDA is usually advisable for several weeks. This regimen

should be followed indefinitely by a nutritious diet supplying one to

two times the RDA.

 

Magnesium, a cofactor for transketolase, should be given as magnesium

sulfate (1 to 2 mL IM of a 50% solution) with thiamine to correct

thiamine resistance and the frequently accompanying hypomagnesemia.

Hyponatremia (see Ch. 12) should be corrected slowly, because rapid

correction may cause central pontine myelinolysis. Recovery from

neurologic deficits is often incomplete in beriberi. In cerebral

beriberi, central pontine myelinolysis may be residual.

 

Thiamine dependency: Several inborn errors of metabolism respond to

pharmacologic doses of thiamine (5 to 20 mg/day). These include a

megaloblastic anemia of unknown mechanism, lactic acidosis due to low

activity of liver pyruvate dehydrogenase, and ketoaciduria due to low

activity of branched-chain keto acid dehydrogenases.