Infantile Beriberi

Infantile beriberi is the clinical syndrome of severe thiamine (vitamin B1) deficiency in infants, which presents acutely with cardiac failure, aphonia or neurological features. It is a medical emergency, with high mortality unless thiamine is given promptly.

It affects exclusively breastfed infants aged 1 to 3 months whose mothers are thiamine deficient, usually from diets based on polished rice or highly processed foods, prolonged food avoidance, hyperemesis or alcohol misuse. It is described in South and Southeast Asia and in refugees and displaced populations, and in infants fed unsupplemented formula or soy preparations.

Maternal deficiency may be subclinical, as thiamine in breast milk falls when maternal stores are low.

Pathophysiology.

Thiamine pyrophosphate is a cofactor for pyruvate dehydrogenase, alpha ketoglutarate dehydrogenase and transketolase. Deficiency impairs oxidative metabolism, so pyruvate and lactate accumulate, causing lactic acidosis.

The heart develops high output failure from peripheral vasodilatation and energy failure of the myocardium. The nervous system is affected by energy failure and lactate accumulation.

• Cardiac form (most common and most severe): tachypnoea, tachycardia, cyanosis, restlessness, vomiting, hepatomegaly, oedema, cardiomegaly and heart failure with metabolic acidosis, sometimes with a loud cry ("shouting").
• Aphonic form: hoarse or absent cry, loss of voice from laryngeal nerve involvement, with or without respiratory features.
• Pseudomeningitic (cerebral) form: nystagmus, ophthalmoplegia, irritability, convulsions, reduced consciousness and bulging fontanelle.
• Gastrointestinal: anorexia, vomiting and constipation.

Red flags.

• Heart failure or shock in a breastfed infant with severe acidosis.
• Seizures, coma or ophthalmoplegia.
• Breastfeeding mother with poor diet or symptoms of beriberi, or siblings with similar illness.

• Clinical, supported by a rapid response to thiamine within hours. Treatment should start before laboratory confirmation.
• Whole blood thiamine diphosphate or erythrocyte transketolase activity (with the thiamine effect), and urinary thiamine, taken before treatment.
• Blood gas, lactate (raised), glucose, electrolytes, chest X-ray (cardiomegaly), ECG (tachycardia, prolonged QT, T-wave changes) and echocardiography (dilated heart with raised output).
• Lumbar puncture, cranial imaging and infection screen to exclude other causes of encephalopathy.

Differential diagnosis. Sepsis, myocarditis, congenital heart disease, supraventricular tachycardia, metabolic disease and mitochondrial disorders, meningitis, pyridoxine dependent seizures, and other causes of lactic acidosis.

Acute treatment.

• Thiamine 25 mg IV over 30 minutes (up to 50 mg in critical illness), with resuscitation facilities available because of rare anaphylaxis, followed by 10 mg IV or IM daily for 1 to 2 weeks, then oral 3 to 5 mg daily for at least 6 weeks. Give thiamine before or with glucose containing fluids.
• Cardiac failure: oxygen, cautious diuretics (furosemide 1 mg/kg IV) and correction of acidosis. Inotropes work poorly until thiamine is given.
• Treat seizures, hypoglycaemia and electrolyte abnormalities, and give respiratory support as needed.
• Response is dramatic within hours for the cardiac form. Neurological recovery may take longer, and residual deficits can persist.

Mother and family.

• Treat the breastfeeding mother with thiamine 100 mg orally daily, improve diet, and continue breastfeeding. Screen siblings.
• Promote diets with thiamine rich foods (whole grains, pulses, meat, fish), and fortification programmes where deficiency is endemic.

Monitoring. Heart rate, respiratory status, lactate, neurological state, weight and development.

Referral and escalation. Refer to paediatric intensive care for shock or respiratory failure, and to public health or nutrition services where cases cluster.