Infantile Beriberi: A Potentially Fatal Condition

Introduction:

Thiamine, also known as vitamin B1, is a water-soluble vitamin with important roles in the development and functioning of the human body. Beriberi was the name given to a major disease that primarily affected prisoners and sailors in the east during the late 1880s causing breathlessness, weakness and loss of sensation in the legs, and cardiac failure. Physicians in Japan observed a potentially fatal disease in breastfed infants that showed symptoms similar to beriberi in adults. It was observed that when these infants were fed cow’s milk, they recovered from the symptoms such as vomiting and edema. Mother’s milk in these cases was considered to be poisonous to the baby. Christian Ejikman who was a Dutch medical officer observed peripheral polyneuritis in chickens fed with polished rice, similar to that in humans. This led him to research the ‘anti-beriberi factor’ that was present in rice bran and was lost in polished rice. It was not until 1926 that thiamine was successfully isolated. Following this discovery, thiamine was synthesized in 1935 and used to fortify cereals and flour along with other micronutrients in the USA, Canada, and other industrial nations nearly eliminating beriberi. Consequently, beriberi was confined to regions where the staple diet consisted of polished rice (Asian countries). Infantile beriberi remains a public health problem contributing to infant mortality to this day.

What Are the Sources and Dietary Requirements of Thiamine?

Some rich sources of Vitamin B1 include pulses like peas and lentils, wholegrain cereals, meat, various nuts and seeds, beans, soy products, etc. Fortified foods such as breakfast cereals and enriched wheat flour account for about half the consumption of thiamine in developed countries. Thiamine needs can be met relatively easily through diverse diets. The required amount of vitamin B1 varies with age and the stage of development, energy requirements, and metabolism. The daily recommended dietary allowance (RDA) of thiamine in children is 0.5 milligrams per day during the first to third years of life, 0.6 milligrams per day in children between the ages of four and eight, 0.9 milligrams per day for children aged 9 to 13 years, and 1 to 1.2 milligrams per day from there on till adulthood. The RDA in adult men and women is 1.1 milligrams per day and 1.2 milligrams per day respectively. During pregnancy and lactation, there is a higher requirement of 1.4 mg/day for increased energy expenditure and growth, and also for thiamine secretion into breast milk. More thiamine is required in individuals consuming a high-carbohydrate diet.

How Is Thiamine Absorbed and Utilized in the Body?

Thiamine is not synthesized in our bodies and needs to be supplied regularly through diet. It is absorbed in the small intestine in its free form by either carrier-mediated transport or passive diffusion into the mucosal cells where it is phosphorylated to form thiamine diphosphate. It circulates in the blood bound to the enzyme transketolase in red blood cells and targets organs that use glucose as their primary energy source like the brain, heart, nerves, and muscles. Free thiamine and phosphorylated forms such as thiamine monophosphate, diphosphate (metabolically active form constituting most of the thiamine in the body), and triphosphate. Thiamine acts as a cofactor for enzyme complexes involved in energy metabolism. A deficiency leads to interrupted or decreased enzyme activity and affects energy production, neural activity, and cell replication, and contributes to the accumulation of lactic acid, oxidative damage, and cell death.

What Are the Risk Factors of Infantile Beriberi?

Factors like decreased nutrient intake, increased demand, impaired absorption, increased nutrient losses, or a combination of these may result in a deficiency. Breastfed infants are prone to deficiency since thiamine-deficient mothers have low thiamine concentrations in breast milk. Thiamine deficiency generally peaks during the third month due to changing metabolic demands and growth. Pregnant women are susceptible to deficiency due to increased demand, and post-partum diet restrictions in certain cultures may also contribute to deficiency. Dietary and cooking practices such as repeated washing, prolonged soaking, polishing of grains, and consumption of foods containing thiaminases such as raw fish increase the risk of thiamine deficiency.

What Are the Characteristics of Thiamine Deficiency in Infants?

Thiamine deficiency has a widely variable presentation but predominantly affects the nervous and cardiovascular systems. Previously two forms of beriberi were described:

• Wet Beriberi - With predominantly cardiovascular manifestations of thiamine deficiency occurring in infants

• Dry Beriberi - Predominantly neurological symptoms including Wernicke’s encephalopathy and Wernicke-Korsakorff syndrome occurring in older children and adults.

However more recently the umbrella term ‘thiamine deficiency disorders’ (TDD) has been suggested and agreed upon to describe the complete spectrum of overlapping symptoms of thiamine deficiency throughout life. Three clinical forms namely aphonic, pernicious or cardiac, and pseudo meningitis forms have been described in infants.

Cardiac Form

1. The earliest signs of infantile beriberi typically occurring between 1 to 3 months of age are non-specific and include:

• Irritability and agitation.

• Refusal to be breastfed.

• Vomiting.

• Incessant crying which is difficult to console.

2. These symptoms may rapidly progress to more serious symptoms such as:

• Tachypnoea and tachycardia (increased respiratory and heart rates).

• Hepatomegaly (enlarged liver).

• Cyanosis (bluish discoloration of the skin or mucous membranes due to oxygen deficit).

• Respiratory distress.

• Acute congestive heart failure with edema and death.

3. Shoshin Beriberi is a fulminant rapidly progressing form of infantile beriberi which typically presents without edema and is characterized by cardiogenic shock with lactic acidosis has been reported in some infants.

Aphonic Form

1. During 4 to 7 months of age, thiamine deficiency can present with a hoarse or soundless cry, caused due to the paralysis of the vocal cords.

2. It is a less severe form but may progress to cardiac failure and respiratory distress in a matter of days or weeks if left untreated.

Pseudo-Meningitic Form

1. It commonly presents between 6 and 12 months of age. It is characterized by nystagmus (involuntary eye movements), ophthalmoplegia (paralysis or weakness of muscles of the eyes), unconsciousness, seizures, muscular fasciculation, etc.

2. Clinical signs of meningitis are present but the cerebrospinal fluid on testing does not show any infection.

Older children and adolescents may present with loss of reflexes and peripheral paresthesia. Ataxia, muscle wasting and pains, and cranial nerve involvement may be present. Wernicke’s encephalopathy presents with the classical triad of cognitive impairment, gait ataxia, and abnormal eye movements in pediatric populations. Signs and symptoms if promptly treated do not lead to permanent damage, but if left untreated it may progress to Wernicke-Korsakoff syndrome with impaired memory, loss of cognitive function, and even coma and death in severe cases.

How Is the Diagnosis of Infantile Beriberi Made?

Due to its varied clinical presentation and considerable overlap of symptoms with other diseases, combined with non-specific symptoms during the early stages a diagnosis of infantile beriberi can be tricky. Non-availability of confirmatory tests due to the high cost and technical skill required, lack of awareness, and its similarity with many other diseases make infantile beriberi a challenging diagnosis. Some tests to assess thiamine levels and functions include:

• Plasma, whole blood, or serum analysis can help determine the thiamine status, but it represents only a small portion of the whole body's thiamine.

• Thiamine diphosphate (TDP) levels give a better picture but do not signify thiamine’s metabolic function.

• Erythrocyte transketolase activity (ETKA) is a functional assay of biological thiamine activity.

• Thiamine is excreted as thiamine monophosphate (TMP) and free thiamine in urine and levels lesser than 40 micrograms per day or 27 micrograms per gram creatinine is considered as thiamine deficiency.

• Neurosonogram with basal ganglia hyperechogenicity can be useful as a first-line screening tool.

• Neurologic involvement in thiamine deficiency can be identified on MRI (magnetic resonance imaging) scans.

What Is the Treatment for Infantile Beriberi?

• Prompt identification and treatment are essential since infantile beriberi can prove to be fatal in a relatively short period.

• Thiamine treatment is safe and economic. Treatment is commenced on clinical diagnosis since waiting on biomarker assays can lead to delay.

• Hence a diagnosis of thiamine deficiency is suspected and treatment is commenced; diagnosis is confirmed through rapid response to parenteral thiamine administration. 50 to 1500 milligrams of thiamine may be administered depending on the symptoms, age, and route of administration.

• Infants having cardiovascular manifestations are treated with 50 to 150 milligrams of parenteral thiamine. Irritability and breastfeeding issues resolve within a few hours and respiratory and cardiac symptoms normalize within 48 hours. Three daily doses of 100 milligrams intramuscular injections of thiamine also showed a revival of cardiac function within 48 hours.

• Neurological symptoms require larger doses and a longer recovery time.

Conclusion:

Thiamine or vitamin B1 is a water-soluble micronutrient that plays a key role in energy metabolism. A deficiency of thiamine, termed beriberi, during the early years of life can prove fatal or may affect neurodevelopment, having far-reaching effects as the child grows. Despite years of attention to infantile beriberi as a public health problem, it continues to contribute to infant mortality in developed as well as developing nations.