bubble_chart Overview

Beriberi, also known as thiamine deficiency, is a condition caused by a lack of vitamin B1 or thiamine. Thiamine is a crucial vitamin involved in sugar and energy metabolism within the body. Its deficiency can lead to functional disorders in the digestive, nervous, and cardiovascular systems. Clinically, beriberi presents in three types: "dry" beriberi, which primarily affects the nervous system and is more common in elderly individuals, often accompanied by wasting symptoms; "infantile" beriberi, which is severe and manifests as acute cardiovascular symptoms, and can be fatal if not treated promptly.

bubble_chart Etiology

Thiamine is abundant in the outer husk and germ of grains, with approximately 90% of the thiamine in grains found in these parts. In many countries and regions where excessive processing removes the husk and germ to produce staple foods, similar cases have been reported in several southern provinces of China, and new cases continue to emerge. Besides improper grain processing, factors such as excessive rice washing, prolonged cooking or heating, or the addition of soda can lead to the loss and destruction of thiamine. A long-term diet high in carbohydrates as the staple food but lacking meat and soy products—an unbalanced diet leading to emaciation due to improper food—can easily cause illness. Various chronic conditions, such as anorexia, can reduce thiamine intake; chronic diarrhea or intestinal parasites can impair thiamine absorption in the duodenum and small intestine; liver dysfunction can interfere with thiamine utilization in the body; hyperthyroidism, infections, high temperatures, intense exercise, pregnancy, and lactation all increase the body's demand for thiamine. Without adequate thiamine supplementation, this can lead to beriberi. Frequent consumption of raw fish and shellfish, which contain thiaminase that breaks down thiamine, can also be a causative factor. Iatrogenic thiamine deficiency may occur in cases of intravenous nutrition without thiamine supplementation, with reports indicating that refractory lactic acidosis can develop after three weeks due to thiamine deficiency.

bubble_chart Pathological Changes

Thiamine is first phosphorylated in the body to form thiamine pyrophosphate, which acts as a coenzyme involved in the oxidative decarboxylation of pyruvate and α-ketoglutarate in carbohydrate metabolism, as well as participating in the ketone group transfer of the pentose phosphate pathway. Thiamine deficiency not only affects carbohydrate metabolism but also involves fatty acid and energy metabolism, leading to the accumulation of pyruvate and lactate in tissues. Additionally, excessive production of alanine in brain cells and reduced generation of aspartate, glutamate, and γ-aminobutyric acid form the basis for the generation and transformation of dysfunction across various systems.

Pathological lesions may manifest as multiple peripheral neuritis, with segmental degeneration and demyelination. The longest nerves in the lower limbs, such as the sciatic nerve, are the first to be affected. Schwann cells exhibit edema, vacuolar degeneration, or even collapse. Cranial nerves (III and VI pairs) and the vagus nerve (recurrent laryngeal nerve) also show degeneration. The pia mater is congested, with pinpoint hemorrhages around small blood vessels. Neuronal loss is observed near the diencephalon and medulla oblongata, accompanied by proliferation of glial cells and vascular endothelial cells. The heart undergoes dilation and hypertrophy due to cardiac insufficiency, particularly in the right ventricle. Microscopically, myocardial fiber cells and interstitial edema are visible, with severe cases showing cellular degeneration and necrosis. Pulmonary blood vessels and systemic peripheral capillaries and small blood vessels also exhibit dilation.

In thiamine deficiency, the increased pyruvate inhibits the activity of choline acetyltransferase, reducing acetylcholine synthesis. Moreover, due to decreased thiamine pyrophosphate production, cholinesterase activity is enhanced, accelerating acetylcholine hydrolysis and impairing nerve conduction. Consequently, gastrointestinal motility slows, and digestive fluid secretion decreases. The disruption of carbohydrate metabolism further reduces cellular function, leading to various digestive symptoms. Pathologically, intestinal distension, mucosal hemorrhage, follicular swelling, and mesenteric lymph node enlargement are observed. Additionally, the liver and kidneys exhibit congestion and fatty degeneration.

bubble_chart Clinical Manifestations

Infantile beriberi is mostly acute, often occurring suddenly with severe and critical symptoms. Early signs may include pale complexion, irritability, restlessness, and edema, which can easily be overlooked. In older children, beriberi resembles that in adults, with edema as the primary manifestation. Initially, swelling is only seen in the pretibial area, and more severe cases may present with edema in the entire lower limbs and face. This is due to reduced appetite, insufficient protein intake leading to hypoproteinemia, combined with cardiac insufficiency.

1. **Gastrointestinal symptoms** Most common in infant patients, symptoms include poor appetite, indigestion, diarrhea with green loose stools, and frequent vomiting. In severe cases, vomiting may resemble coffee-ground material. Choking coughs may also occur. Other symptoms include abdominal distension, fullness, and constipation, though the abdomen remains soft. Hepatomegaly is present in most cases.

2. **Neurological symptoms** The hallmark of infantile beriberi is that neurological paralysis begins with the cranial nerves, with prominent central nervous system symptoms. Manifestations include apathy, blank staring, or persistent drowsiness, drooping eyelids, extreme flaccidity of neck and limb muscles leading to head tilting backward, inability to grasp, weak sucking, absence of crying, and diminished or absent tendon reflexes. Severe cases may develop muscle atrophy, ataxia, and loss of deep sensation and reflexes. Infants aged 8–10 months are prone to increased intracranial pressure and pseudomeningitis symptoms during this stage, eventually progressing to unconsciousness and convulsions. Death may result from cerebral edema and respiratory failure. Cerebrospinal fluid shows only slightly elevated protein without other abnormalities. Before any neurological paralysis occurs, most infants first exhibit hoarseness, aphonia, or silent crying due to recurrent laryngeal nerve paralysis. Some severe cases may show epileptiform EEG patterns after recovery, suggesting possible sequelae.

In older children, neurological damage primarily manifests as multiple peripheral neuropathies. Sensory nerve impairment first affects touch, followed by pain, and finally a sensation of swelling, numbness, prickling, or burning. The gastrocnemius muscle is notably tender to touch. Sensory impairment is usually bilateral and symmetrical, distributed in a stocking-like pattern. Superficial sensory decline precedes deep sensory dysfunction. Motor nerve paralysis typically follows sensory impairment, starting in the lower limbs and progressing upward. Paralysis of the lower limbs begins in the toes, with difficulty in dorsiflexion due to peroneal nerve damage, causing unsteady gait and frequent falls. Severe cases may present with foot drop and walking difficulties. Upper limb paralysis starts in the fingers, with wrist drop due to earlier and more severe extensor muscle involvement. Muscle weakness and atrophy follow, making squatting difficult. Tendon reflexes diminish or disappear. Central nervous system damage in older children resembles that in adults, presenting as cerebral type (Wernicke’s encephalopathy), with emotional and psychological abnormalities such as nervousness, irritability, or depression, and poor concentration. Some patients may also experience vertigo, ocular tremor, and ataxia, suggesting cerebellar and vestibular dysfunction.

3. **Cardiovascular symptoms** Infant patients exhibit dysphoria, tachypnea, pale complexion with perioral cyanosis. Pulmonary congestion causes cough, while peripheral circulatory stasis leads to purplish skin mottling. Infants aged 2–4 months are prone to acute heart failure, presenting as "fulminant cardiac beriberi." It often occurs suddenly after feeding or upon waking, with sharp crying followed by cold sweats, hoarse cries, cyanosis of extremities and lips, irregular breathing, muffled heart sounds, cold limbs, and hypothermia. Without timely treatment, death may occur rapidly.

In older children, the initial stage presents with palpitations only after activity or emotional excitement. If the condition progresses, palpitations and tachypnea occur even at rest. A few children may suddenly develop heart failure after excessive fatigue or overeating.

Physical examination reveals an enlarged cardiac dullness border in both infants and older children, along with epigastric pulsations. The heart rate is significantly increased, sometimes exhibiting a fetal rhythm or gallop rhythm. A systolic murmur can be heard at the apex, and the pulmonary stirred pulse second sound is more pronounced. The liver and spleen are enlarged due to congestion. Diastolic blood pressure decreases and may fall below 8 kPa (60 mmHg), while systolic blood pressure shows little change.

The X-ray examination reveals an enlarged heart on both sides, with a predominant enlargement to the right. The electrocardiogram shows increased amplitudes of P waves and QRS complexes. The T waves are flattened or inverted, with a prolonged QT interval. Infant patients may exhibit hypotension, and occasional sinus arrhythmia may be observed. The pulse tracing displays a dicrotic pulse.

This condition is only seen in newborns. It occurs when the mother consumes mostly white rice, lacks sufficient meat in her diet, or has other predisposing factors leading to thiamine deficiency. At birth, the infant presents with generalized edema, hypothermia, weak sucking, recurrent vomiting, limp limbs, prolonged sleepiness, and weak crying. If switched to cow's milk or the breast milk of a healthy individual, the vomiting ceases, urine output gradually increases, edema subsides, and all other symptoms disappear completely. Occasionally, the infant may appear normal at birth but develops symptoms after 4–5 days, with the mother showing obvious signs of the condition.

bubble_chart Diagnosis

The symptoms of infantile beriberi are highly variable, making early diagnosis difficult. In addition to clinical manifestations, attention should be paid to inquiring whether the residence is in a rice-producing area, whether there has been a recent beriberi epidemic, feeding history, and any suspicious symptoms in the nursing mother. Clinically, the following diseases should be excluded, such as viral encephalitis, cerebral {|###|}membrane{|###|}itis, acute laryngitis, hand-foot {|###|}convulsion{|###|} disorder, acute poisoning, {|###|}tetanus{|###|}, congenital heart disease, etc.

The clinical manifestations of beriberi in older children also vary greatly among individuals. Dietary habits, the presence of chronic wasting diseases, participation in labor or physical exercise should be inquired about. A detailed physical examination is also necessary to prevent misdiagnosis of {|###|}fistula disease{|###|}.

Laboratory diagnosis can include the following methods:

(1) Thiamine load test: Oral administration of 5mg or intramuscular injection of 1mg vitamin B₁, followed by collection of 4-hour urine to measure the amount of thiamine excreted. Normally, it exceeds 100μg, whereas in beriberi patients, it is below 50μg or even zero.

(2) Measurement of pyruvic acid and lactic acid levels in the blood. In beriberi patients, these levels are significantly elevated, aiding in diagnosis. Moreover, most cases show a marked decrease in carbon dioxide combining power.

(3) Determination of erythrocyte transketolase activity. In beriberi patients, the activity of this enzyme is significantly reduced.

Among the above tests, the latter two results are more reliable, as they can estimate the actual degree of thiamine deficiency from the metabolic disturbances caused by thiamine deficiency. The load test only reflects the immediate level after thiamine intake and does not indicate thiamine storage and distribution in tissues, nor does it reflect the {|###|}generation and transformation{|###|} changes caused by thiamine deficiency.

In cases where laboratory diagnosis is not feasible, administering vitamin B₁ as a diagnostic treatment for suspected cases is also a safe and reliable method.

bubble_chart Treatment Measures

During the first week of illness, vitamin B₁ should be administered daily at a dose of at least 10 mg. Starting from the second week until clinical symptoms disappear, the daily dose should be 3–5 mg. The maintenance dose thereafter is 1–5 mg per day. When an infant has beriberi, the nursing mother, whether or not she shows symptoms of thiamine deficiency, should also be treated simultaneously with an oral dose of 50 mg of vitamin B₁ daily, which should be reduced to the maintenance dose after the infant recovers. Since patients often suffer from deficiencies in other B vitamins, oral administration of a vitamin B complex or yeast tablets should also be given concurrently.

In cases of acute cardiac beriberi, immediate emergency treatment is essential. Commonly used fast-absorbing and long-acting thiamine derivatives such as prosultiamine or fursultiamine (which are not destroyed by thiaminase in the body and have low toxic reactions) are administered, with an initial intravenous dose of 50–100 mg. This should be repeated every 3–4 hours until heart failure is controlled, after which the dose should be reduced or changed to maintenance therapy 2–3 times daily for one week. For symptoms such as dyspnea and acidosis, oxygen inhalation and intravenous infusion of an appropriate amount of 5% sodium bicarbonate should be administered as symptomatic treatment. Intravenous injection of hypertonic glucose is contraindicated in cardiac beriberi, as it may lead to sudden cardiac arrest. Similarly, respiratory stimulants such as nikethamide and lobeline should not be injected to avoid increasing oxygen consumption and exacerbating spasms. The use of digitalis to control beriberi heart failure is also harmful.

With the above treatment, symptoms such as anorexia, edema, and heart failure may disappear within 24 hours, but peripheral neuropathy and myocardial damage often take weeks to months to gradually recover. After discharge, a maintenance dose of vitamin B₁ should be given to prevent relapse.

Hormones can elevate blood sugar levels and worsen the condition by inhibiting the oxidation of lactate and pyruvate, so they are also contraindicated.

bubble_chart Prevention

The human body cannot synthesize thiamine, and its reserves are limited. Although intestinal bacteria can produce thiamine, the amount is minimal and primarily in the form of pyrophosphate esters, which are poorly absorbed by the intestines. Therefore, it is essential to consume vitamin B₁ daily from food.

One crucial measure to prevent beriberi is to strengthen hygiene supervision and guidance in food processing to minimize the loss of thiamine during grain milling. Additionally, nutrition and hygiene education should be enhanced, especially in rice-producing regions and among populations relying on rice as a staple food, emphasizing the importance of dietary diversity and balanced nutrition.

Among natural foods, pork contains the highest amount of thiamine per 100 grams, ranging from 0.5 to 1.2 mg (other meats contain 0.1–0.2 mg), followed by pork liver (0.4 mg), soybeans (0.8 mg), brown rice (0.34 mg), and polished rice (0.13 mg). Vegetables, fruits, and eggs contain no more than 0.1 mg of thiamine per 100 grams. Thus, meat and soy products are excellent sources of thiamine. Pregnant women, nursing mothers, adolescents, and manual laborers should increase their intake of these foods. In beriberi-endemic areas, preventive doses of vitamin B₁ can be distributed for daily consumption.

The daily requirement of vitamin B₁ is 0.5 mg for infants, 1–1.5 mg for children, and 2–3 mg for pregnant and lactating women.

Adrenocortical hormones and adrenocorticotropic hormone can counteract the physiological effects of thiamine, hindering the oxidation of pyruvate. Excessive folic acid or niacin may impair the phosphorylation of thiamine in the liver. Diuretics can increase the excretion of thiamine. These factors should be considered to avoid the occurrence or exacerbation of iatrogenic beriberi.