eMedicine Specialties > Pediatrics: General Medicine > Nutrition

Beriberi

Author: Simon S Rabinowitz, MD, PhD, Professor of Clinical Pediatrics, New York Medical College; Chairman, Chief and Medical Administrator, Department of Pediatrics, Chief, Pediatric Gastroenterology and Nutrition, Richmond University Medical Center
Coauthor(s): L Arturo Batres, MD, Assistant Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, The Children's Hospital of the King's Daughters; Sheela Moorthy, MD, Staff Physician, Department of Pediatrics, Richmond University Medical Center
Contributor Information and Disclosures

Updated: Sep 18, 2009

Introduction

Background

In 1630 a Dutch physician, Jacobus Bonitus, observed in Java, "a very troublesome affliction, ...called by the inhabitants Beri-beri (which means sheep), those, whom this same disease attacks, with their knees shaking and the legs raised up, walk like sheep."

In the last 100 years, 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.

How a single vitamin deficiency can have such diverse patterns of presentation is not fully understood, but genetic differences in the 3 enzymes that use thiamine are likely to play a large role. Other potential explanations include the coexistence of other vitamin or dietary deficiencies; simultaneous comorbidities, stressors, or both; and variations in tissue stores or turnover of the vitamin. During an Israeli outbreak of beriberi in late 2003, 600-1000 infants consumed a thiamine-deficient formula, yet only a small number manifested clinical manifestations.

Although the thresholds and prevalence varies in both developed and underdeveloped countries, beriberi is presently found in situations outside of the normal protective measures of modern society. Also, unusual physiologic conditions in which beriberi could have been predicted have been documented. Finally, chance circumstances in which thiamine deficiency is fully unanticipated have also been recognized. Dietary thiamine deficiency can be caused by an overall poor nutritional intake, by dietary customs that rely heavily on inadequate food sources (eg, milled rice), and, rarely, by consuming foods that contain thiaminases or antithiamine compounds.

Because its husk is an important source of thiamine, changes in rice processing may contribute to a higher rate of thiamine deficiency unless this risk factor is recognized. A cohort at particularly high risk are alcoholics who have poor nutrition and because alcohol also impairs thiamine absorption. A newly appreciated cohort of individuals with thiamine deficiency are patients who have had bariatric surgery.¹

In 1998, the Institute of Medicine of the National Academies published the recommended dietary intake of thiamine and other B vitamins for males and females (from infants to the elderly).² Also, a comprehensive monograph on beriberi was commissioned by the World Health Organization; it recommends that the term beriberi be replaced by thiamine deficiency.³

For more information regarding the cardiovascular and neurologic manifestations encountered in adult patients, see the eMedicine article Beriberi (Thiamine Deficiency).

Pathophysiology

Thiamine mainly functions as thiamine pyrophosphate (TPP), which serves as a prosthetic group or cofactor for 3 enzymes essential to carbohydrate metabolism. These enzymes all use thiamine's thiazole ring to activate and transfer a 2-carbon unit (aldehyde), which provides precursors for other synthetic pathways and also provides energy for the cell. The enzymes catalyze decarboxylation of pyruvate and of ketoglutarate and the transketolation reaction in the pentose phosphate pathway.

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. Alpha ketoglutarate dehydrogenase is essential for the Krebs cycle, which yields even greater amounts of ATP (energy) and additional neurotransmitters (GABA and glutamate). A reduction of transketolase activity compromises the hexose monophosphate shunt. This yields decreased amounts of nicotinamide adenine dinucleotide phosphate (NADPH) formation which is required for intramitochondrial electron transport and depletes nucleic acid precursors.^4,5

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. The exact biochemical defect responsible for the clinical manifestations of cardiac (wet) beriberi or its acute form, Shoshin beriberi (from the Japanese, meaning "sudden collapse"), is not yet fully elucidated. Cardiac dysfunction may simply be compromised by myocardial tissue edema and energy depletion.

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.

Deficiency of thiamine affects the cardiovascular, muscular, nervous, and GI systems. The body stores of thiamine are minimal, and the duration of thiamine reserves is unknown. In one study, deficiency was detected after approximately 6 weeks without thiamine. In another study of healthy young men who consumed less than 0.2 mg of thiamine daily, urinary excretion of thiamine stopped within 18 days. Case studies have suggested that fatal deficiency can develop in as little as 3 weeks without thiamine intake.

Despite the widespread fortification of many foods and infant formulas with thiamine, clinicians must remain aware of the signs and symptoms of beriberi, a life-threatening, but rapidly reversible, condition.

Frequency

United States

The incidence of beriberi is unknown. Although all of the following published cohorts were not based on American patients, they could have occurred within the United States.

• Although the vast majority of clinical cases are encountered in individuals with alcoholism, beriberi outbreaks have been described in other poorly nourished cohorts. East Asian immigrants who maintain their typical diet are particularly vulnerable.
• Beriberi has been described in patients with GI diseases that include malnutrition, malabsorption syndromes (eg, human immunodeficiency virus [HIV] enteropathy⁶ ), and hyperemesis gravidarum.{Ref5} It has also been reported in hypermetabolic conditions such as lymphoma.
• In the late 1980s, a shortage of multivitamin infusion occurred in the United States due to reduced production.{Ref6} As a result, numerous patients dependent on total parenteral nutrition (TPN) developed beriberi, which was rapidly reversed by intravenous thiamine. Ironically, thiamine was readily available despite the multivitamin shortage.
• One review cited more than 100 reports that described dry beriberi following bariatric surgery.² Stringent criteria summarized 84 cases that included 2 or more of the following: mental status changes, eye movement abnormalities, cerebellar dysfunction, and dietary deficiency. Gastric bypass or a restrictive procedure was performed in 80 cases (95%). Admission occurred within 6 months of surgery in 79 cases (94%). Frequent vomiting was a risk factor in 76 cases (90%) and had lasted for a median of 21 days at admission. Intravenous glucose administration without thiamine was a risk factor in 15 cases (18%). Brain MRI identified characteristic lesions in 14 cases (47%). Incomplete recovery was observed in 41 cases (49%); memory deficits and gait difficulties were frequent sequela. As suggested by the authors, surgeons, emergency room physicians, and health care providers need to be aware of the possibility of beriberi in patients who have experienced prolonged emesis after gastric bypass surgery.
• In late 2003, a beriberi outbreak was seen among normal Israeli infants.^7,8 The cause of the deficiency was a manufacturing omission of thiamine in a brand of soy-based formula exclusively marketed in Israel. Tragically, 2 of the earliest-affected infants died before the etiology was recognized. MRI findings of this cohort are summarized below. Follow-up neurodevelopment studies were conducted on 20 of these infants; learning disabilities were reported, including delayed language development compared with infants fed other sources of milk and matched for age, sex, and maternal education.
• An intriguing hypothesis that has recently been published by several groups links subclinical or unrecognized thiamine deficiency to adult congestive heart failure. Diuretics were found to result in increased thiamine excretion and to predispose to a relative deficient state. In a study from Toronto, one third of adults hospitalized with congestive heart failure had thiamine deficiency, compared with 12% of controls.⁹

International

• The prevalence of beriberi is much higher in East Asian countries because of the consumption of milled rice. Thiamine is contained in the outer coat of rice, and polishing destroys it. In the same countries, the custom of eating raw fish further increases the potential for deficiency.
• Breastfed infants whose mothers have thiamine deficiency develop an infantile form of beriberi.
• The same socioeconomic factors that yield beriberi in the West do so with much greater prevalence in East Asia. A study done in Indonesia revealed the prevalence of thiamine deficiency among low-income families to be as high as 66%.¹⁰ A study conducted in a group of Karen women from a refugee camp on the Thailand-Burma border revealed that up to 58% of these women were thiamine deficient 3 months postpartum, despite what appeared to be adequate dietary thiamine supplements.¹¹
• Outbreaks have been described in prisons,¹² drug rehabilitation centers,¹³ rural, agrarian communities, and in ships kept out at sea too long.
• A familial form of thiamine deficiency with mitochondrial myopathy has been described in Japan.^14,15
• A report from Brazil described an outbreak of dry beriberi that lasted from 2006-2007 and included more than 1000 cases and 30 deaths. Most individuals were male laborers who were working in a region of the country where traditional agriculture was replaced to accommodate logging and mining industry. The Brazilian ministry of health points out that the previous outbreak in the country, around the turn of the century, occurred in conjunction with the expansion of the rubber industry in the Amazon. This experience suggests that when local factors disturb the established social, economic, or agricultural balance, the potential for beriberi increases, and that those with poor nutrition, especially those who also abuse alcohol, represent the most vulnerable targets.

Mortality/Morbidity

Mortality is rare and is usually restricted to wet beriberi (cardiac) that goes undiagnosed for too long and, hence, can not be treated. Morbidity is also rare and is usually seen in dry beriberi (neurologic) that is treated so late in the course of the illness that some residual neurologic deficits remain. In both situations, the timely recognition of the signs and symptoms of beriberi can result in thiamine replacement, which rapidly reverses the cardiovascular and neurologic dysfunction.

Race

The prevalence is highest in cultures that depend on a high proportion of their calories from foods that have poor thiamine content, such as milled rice. 

Sex

Beriberi can affect both genders, although alcoholism (a major risk factor) is more prevalent in males.

Age

Beriberi is predominantly observed in adults and infants aged 1-4 months (infantile beriberi).

Clinical

History

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 beriberi
  • This 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:
    • 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.
    • 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.
    • 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.
• Wernicke-Korsakoff syndrome
  • This is an autosomal recessive genetic disease seen most often in individuals of European descent.
  • Affected patients have transketolases that bind thiamine pyrophosphate 10 times less tightly than normal; thus, the serum levels required to yield maximum enzyme activity are higher. Patients with Wernicke-Korsakoff are thus symptomatic with much less severe thiamine depletion.
  • This syndrome occurs most often in individuals with alcoholism who are malnourished. It is often precipitated by administration of glucose because excessive carbohydrate metabolism exacerbates a subclinical thiamine deficiency.
  • Clinically, it combines features of both Wernicke encephalopathy and Korsakoff psychosis.
• Subclinical thiamine deficiency
  • This deficiency is seen in people with high carbohydrate intake and low thiamine intake.
  • Other at-risk groups include those with increased thiamine requirements because of raised physiological or metabolic demands. Clinical scenarios include pregnancy and lactation, heavy physical exertion, intercurrent illness (eg, cancer, liver diseases, infections, hyperthyroidism), and surgery.
  • This deficiency is rarely encountered in patients with increased losses, such as those seen with dialysis, chronic diuretic use, and malabsorption.
  • Symptoms are usually mild, with anorexia often the presenting symptom. Anorexia is regarded to be a protective phenomenon because continued intake of a high-carbohydrate diet could be detrimental.
  • Other early symptoms include weakness, aching, burning sensation in the hands and feet, indigestion, irritability, and depression. After 6-8 weeks, the only objective signs at rest may be a slight fall in blood pressure and moderate weight loss. After 2-3 months, apathy and weakness become extreme and calf muscle tenderness develops. Also, loss of recent memory, confusion, ataxia, and, sometimes, persistent vomiting occur.
  • Pediatric associations include growth restriction and sudden infant death syndrome (SIDS).

Physical

• Wet beriberi (cardiac)
  • Edema
  • Waxy skin
  • Vomiting
  • Widened pulse pressure
  • Systolic flow murmur
  • Gallop rhythm (third heart sound); best heard in left-lateral position during inspiration
  • Jugular venous distension
  • Tachycardia
  • Cardiomegaly
  • Pallor
  • ECG changes (prolonged QT, T-wave inversion, low voltage)
• Acute fulminant cardiovascular beriberi (Shoshin beriberi or occidental beriberi)
  • Breathlessness, cyanosis
  • Wet crackles in lower lung fields
  • Classic heart failure
• Dry beriberi (paralytic or nervous)
  • Pallor
  • Wasting
  • Listlessness
  • Tachycardia
  • Hepatomegaly
  • Symmetric peripheral neuropathy
  • Symmetric paresthesias, especially of the distal extremities, with diminished touch sensation
  • Weakness (starting with feet)
  • Loss of ankle and knee reflexes
  • Normal vibration and pain sensation
• Wernicke disease
  • Irritability, forgetfulness
  • Ataxia
  • Mental confusion
  • Nystagmus (horizontal more common than vertical)
  • Ptosis
  • Ophthalmoplegia
  • Delirium
  • Coma
• Korsakoff psychosis
  • Retrograde amnesia
  • Inability to learn
  • Confabulation
• Wernicke-Korsakoff syndrome - Combined features of both Wernicke disease and Korsakoff psychosis
• Infantile beriberi
  • Physical findings depend on the form but usually begin with nonspecific early findings, including the following:           
    • Fatigue
    • Anorexia
    • Headaches
    • Irritability, fatigue
  • The physical findings in acute cardiac infantile beriberi are similar to those found in Shoshin beriberi, often with cyanosis.
  • The physical findings in aphonic infantile beriberi include hoarseness that progresses to a complete loss of crying.
  • The physical findings in pseudomeningeal infantile beriberi include nystagmus, muscle twitching, bulging fontanelle, convulsions and coma.

Causes

• Beriberi is caused by thiamine deficiency, which can be the result of different physiologic, dietary, and environmental factors. 
• Frequently, more than one risk factor is present.

• Search for CME/CE on This Topic »

• Beriberi (Thiamine Deficiency) (Endocrinology)
• Nutritional Neuropathy (Neurology)
• Vitamin A Deficiency (Endocrinology)
• Alcohol (Ethanol) Related Neuropathy (Neurology)

• Benfotiamine, a Synthetic S-acyl Thiamine Derivative, has Different Mechanisms of Action and a Different Pharmacological Profile Than Lipid-soluble Thiamine Disulfide Derivatives