Pediatric Beriberi

The cause of beriberi was determined to be deficiency of thiamine (vitamin B1), a water-soluble and heat-labile vitamin required for carbohydrate metabolism. Thiamine is essential for most vertebrates and some microorganisms. Beriberi has 2 main forms in humans, depending on the system of maximum involvement. Wet (edematous) beriberi is a cardiovascular dysfunction that is usually chronic but may have an acute presentation. Dry beriberi is a multifocal peripheral and/or central neurologic dysfunction, which includes Wernicke encephalopathy and Korsakoff syndrome. Often times, patients present with involvement of both systems.

Pathophysiology
Thiamine mainly functions as thiamine pyrophosphate (TPP), which serves as a prosthetic group or cofactor for 3 enzymes essential to carbohydrate metabolism. Pyruvate dehydrogenase is the last step in the catabolism of glucose for energy, glycolysis, and yields acetyl coA, which is required to synthesize acetylcholine, an important neurotransmitter.

Impaired energy production, increased manufacturing of free radicals, decreases in neurotransmitters, and possible N -methyl-D-aspartate (NMDA) receptor–mediated toxicity have been hypothesized to yield the neuronal injury seen in dry beriberi.

Sources of Thiamine
Thiamine is not widely distributed in high concentrations; consequently, many foods are now routinely fortified with it. Rich natural sources include whole grains, lean pork, peas, spinach, and legumes. Very little thiamine is present in fats, oils, and refined sugars. It is destroyed by heat, pasteurization, and ionizing radiation. Freezing does not affect the bioavailability of thiamine; however, it is insoluble in alcohol. The risk of beriberi increases in individuals who consume a diet high in thiaminase rich foods (eg, raw freshwater fish or shellfish, ferns), a diet high in antithiamine factors (eg, tea, coffee, betel nuts), or both.

Clinical Presentation
Thiamine deficiency has a wide range of clinical presentations. Although clinical overlap is common, the basic phenotypes are as follows:

Wet beriberi
This phenotype affects the cardiovascular system and is divided into acute and chronic forms.

In acute wet beriberi or Shoshin beriberi, the predominant injury is to the heart, and rapid deterioration occurs because of the heart’s inability to maintain function.
Presenting symptoms include tachycardia, low diastolic pressure, cardiomegaly, pulmonary edema, and cyanosis. Wet beriberi is characterized by elevated lactic acid levels. This condition can be readily reversed with thiamine infusion, if administered early.

Chronic wet beriberi with high-output cardiac failure has 3 stages.

• Initially, peripheral vasodilatation occurs, yielding high-output cardiac failure.
• Then, the progression of vasodilatation is perceived by the kidney as a relative loss of volume. The ensuing activation of the renin angiotensin system produces greater salt and water retention.
• Consequently, further fluid overload results in peripheral edema and pulmonary effusions.

Cardiac overuse injury that occurs in the above setting results in tachycardia,hypertension, and chest pain.
Thyrotoxicosis, a more common cause of high-output cardiac failure, is always among the differential diagnoses.

Dry beriberiThis phenotype affects the neuromuscular system.

• Polyneuritis and symmetric, ascending paralysis of the peripheral nerve systems predominate.
• The sensory system is affected first, followed by the motor and autonomic systems.
• Typically, tactile sensation is the first to be lost, followed by pain, and, finally, temperature.
• Paresthesia and hyperesthesia usually begin with the lower extremities and gradually involve the upper extremities and perioral area.
• Deep tendon reflexes are lost, calf muscles become painful, and foot drop and, eventually, wrist drop occur.
• If untreated, progressive weakness, wasting of muscles, and, ultimately, complete paralysis occur.
• Encephalopathy is an alternative mode of presentation, with vomiting, disorientation, horizontal nystagmus, palsies of the eye movements (ophthalmoplegia), ataxia, and progressive mental impairment.
• Korsakoff syndrome is a more ominous condition that usually precludes complete recovery. Confusion is followed by the loss of recent memory and confabulation, which is the creation of accounts of events to cover up the loss of memory.

Infantile thiamine deficiency
This occurs in various forms and typically affects breastfed infants whose mothers had beriberi.
Early on, the infant is constipated, crying, restless, and has emesis.
Three forms are recognized:

1. The pure cardiologic or pernicious form is common in infants aged 1-3 months. They present with cyanosis and features of acute cardiac failure. Infants usually die within 2-4 hours, but this type of deficiency responds very rapidly to thiamine.
2. The aphonic form is seen in infants aged 4-6 months. This milder form causes loss of voice due to paralysis of the vocal cords.
3. The pseudomeningitic form is encountered in infants aged 7-9 months. It presents with clinical signs of meningitis, but cerebrospinal fluid findings exclude infection. Vomiting, sweating, and seizures may be present.

Diagnosis
The most rapid, and thus the best diagnostic test for beriberi in urgent situations, is observing a clinical response to administration of intravenous thiamine (few hours duration).[19]
The most reliable in vitro laboratory tests involve measurement of whole blood or erythrocyte transketolase activity.

An enhancement of enzymatic activity from the in vitro addition of thiamine pyrophosphate (TPP) is referred to as the TPP effect.
An increase in the enzymatic activity of more than 15% strongly supports the diagnosis of thiamine deficiency.
A depressed blood level of thiamine can be seen.

Management

• Monitor patients with cardiac failure in an intensive care unit.
• Because beriberi often presents with other vitamin B deficiencies, administer a complete vitamin B complex.
• After the high-output state has been addressed with thiamine, patients can go into standard congestive heart failure and, thus, may require ongoing cardiology consultation, possibly remaining in an intensive care unit.

Diet

Patients with lethargy, confusion, and severe heart failure need to be kept on a diet of nothing by mouth (NPO) to prevent aspiration.
Dietary sources of thiamine must be emphasized along with ongoing supplementation.