BERIBERI
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| SOURCES AND METABOLISM OF THIAMINE (VITAMIN B1) |
Beriberi is a nutritional deficiency state that is caused directly by a lack of thiamine (vitamin B1) in one’s diet or by a lack of proper absorption of the vitamin. A rare form of acquired thiamine deficiency occurs after the ingestion of thiaminase, an enzyme that cleaves thiamine into a nonfunctional state. These cases are exceedingly rare and are considered to occur after an accidental poisonous ingestion of a source high in thiaminase. Thiamine deficiency is a rare occurrence in most of the world but is still seen in people whose food supply is based primarily on polished rice. The other major cause of the disease is alcoholism. Alcoholics who obtain most of their caloric intake from alcohol may be deficient in a multitude of B vitamins including thiamine. Thiamine deficiency may be seen in neonates and infants who are breast feeding from mothers with borderline thiamine deficiency. The principal food sources of thiamine are fresh meats, liver, whole wheat bread, and vegetables. Nonpolished brown rice is also a good source of thiamine. Thiamine is absorbed in the gastrointestinal tract in the proximal jejunum.
Thiamine
deficiency has been reported in cases of short gut syndrome and after bariatric
surgery in which large parts of the jejunum are bypassed and absorption of
thiamine is dramatically decreased. Most of these cases were complicated by the
fact that patients were not following their prescribed diets. Beriberi has also
been reported in patients with human immunodeficiency virus infection and in
some people taking longterm furosemide therapy without adequate thiamine
intake. Furosemide has been shown to increase the rate of excretion of thiamine
from the kidneys.
Thiamine
is a water-soluble vitamin that is critical in the formation of the energy
storage molecule, adenosine triphosphate (ATP). Thiamine is crucial for the
proper functioning of both glycolysis and the Krebs cycle. The U.S. Nutrition
Board of the Institute of Medicine, National Academy of Sciences, has
designated 1.2 mg/day of thiamine as the normal recommended daily intake for
men and 1.1 mg/day for women.
Clinical Findings: The disease is most frequently seen in Asia,
where polished rice is one of the main food sources. Alcoholics are at very
high risk for development of this vitamin deficiency. There is no race or
gender predilection, and it can occur in all people. The clinical findings in
beriberi are highly variable and are dependent on the level of deficiency and
the patient’s underlying comorbidities. The organ systems most commonly
involved are the central nervous system (CNS) and the muscular system. Two
major forms of beriberi occur, although there is much overlap. Dry beriberi is
a form of the disease in which the CNS symptoms predominate. Wet beriberi is
the form in which the predominant symptoms are salt retention and congestive
heart failure. Infantile beriberi is rare but is manifested by a combination of
dry and wet beriberi with severe CNS depression, heart failure, and sudden
death.
The
first signs and symptoms of dry beriberi are typically those of a peripheral
neuropathy and of muscle disease involving both skeletal and smooth muscle. Dry
beriberi typically manifests with increasing fatigability, muscle weakness,
paresthesias, a decrease in deep tendon reflexes, and loss of sensation. As the
disease progresses, patients may develop a foot or wrist drop (flaccid
paralysis). The lower extremity is typically affected before the upper. Loss of
muscle mass may be prominent. Elevated levels of creatinine phosphokinase are
seen, as well as a creatinuria. Weakness is profound.
Wet
beriberi predominantly affects the muscle tissue, particularly the cardiac
system. The end stage is high-output cardiac failure; without treatment, death
follows. Beriberi rarely causes death if the diagnosis is made and proper treatment
is instituted before end-stage heart failure sets in. Patients with wet
beriberi experience a decrease in diastolic blood pressure and minimal change
in systolic pressure, resulting in an overall increase in the pulse pressure.
Tachycardia is prominent. As heart failure develops, pulmonary edema and
fluid retention occur, causing dependent edema and difficulty breathing.
Cyanosis may occur from poor oxygenation. Laboratory testing shows an increased
QT interval on electrocardiography and increased serum levels of lactic acid,
pyruvate, and α-ketoglutarate. Chest radiography shows an enlarged
heart with dilation of the right side and pulmonary congestion, edema, or both.
The
skin findings of beriberi are not specific, but when seen in conjunction with the
rest of the clinical picture, they can definitely help make the diagnosis. The
cutaneous findings of wet beriberi consist of cyanosis of the skin with
variable amounts of peripheral edema. The skin has a waxy appearance and feel.
Cutaneous pallor is prominent and, along with the cyanosis, gives the patient
an ill appearance. Pallor is a common skin finding in dry beriberi as well.
Patients may also present with accidental traumatic injuries to their
extremities related to lack of sensation from the peripheral neuropathy. Hair
loss has been reported, but most believe that this is secondary to a
combination of niacin and thiamine deficiency.
The
excretion of thiamine via the kidneys is markedly decreased in beriberi.
Normally, 70 to 150 µg of thiamine is excreted per gram of creatinine. In
beriberi, that level can drop to zero.
Histology: Biopsy specimens of the skin in patients with beriberi
are of no clinical usefulness. A skin biopsy from an area of cyanosis or pallor
shows normal skin. A biopsy from one of the waxy areas may show variable mild
degrees of acanthosis and parakeratosis. A muscle biopsy shows vacuolization
and hyalinization of the muscle fibers. An inflammatory process may be present
that can cause varying degrees of necrosis of the muscle. The muscle fibers may
show diffuse or focal fiber necrosis. These changes are most prominent in the
cardiac muscle. In patients who develop Wernicke’s syndrome, postmortem
examinations of the brain have revealed small hemorrhages within the
hypothalamus and upper brainstem. Peripheral nerve tissue shows noninflammatory
degeneration of the neurons with atrophy and chromatolysis. This can occur in
the neurons of the peripheral nervous system and the CNS. Pathogenesis: All
forms of beriberi are caused by a nutritional deficiency of thiamine. Thiamine
is a critical vitamin that is needed for carbohydrate metabolism. Thiamine is
the precursor for thiamine pyrophosphate (TPP). It is converted to TPP by the
addition of one ATP molecule. TPP is needed as a cofactor for the proper
function of many metabolic pathways. TPP helps transfer an aldehyde group from
a donor to a beneficiary chemical structure. Three major energy-producing
pathways are modulated by TPP: glycolysis, the Krebs cycle, and the pentose
shunt (hexose monophosphate shunt). The hexose monophosphate shunt is important
in producing other cofactors that play important biochemical roles for donation
of hydrogen. The overall chemical state that occurs in patients with thiamine
deficiency is a lack of ability to produce sufficient quantities of cellular
ATP. This lack of the main source of energy for the cell results in the
clinical findings. The nervous tissue and muscle tissue are particularly prone
to damage from failure to produce sufficient ATP.
It
has been estimated that 3 to 6 weeks of a thiamine-free diet in an average
human is sufficient to cause development of the initial signs and symptoms of
beriberi.
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| CLINICAL MANIFESTATIONS OF DRY AND WET BERIBERI |
Treatment: Therapy consists of supplementation of the patient’s diet with 50 mg/day intramuscularly of thiamine until the symptoms resolve. Treatment should also include other B-complex vitamins, because many patients who are deficient in one B vitamin also have low levels of the others. A nutritionist should be consulted to educate the patient on the need for a proper diet and how to achieve this. Alcoholics are prone to recurrence of beriberi and should be encouraged to participate in alcohol abstinence programs and to take a daily multivitamin supplement. The symptoms rapidly reverse on replacement of thiamine.
