Thiamine Deficiency

Etiology and Risk Factors

Dietary Causes

• Breastfed Infants: Infantile thiamine deficiency typically occurs in breastfed infants of thiamine-deficient mothers.
  • Mothers may be asymptomatic or have subclinical deficiency.
  • Maternal diets based exclusively on polished rice are a primary risk factor, as milling removes the thiamine-rich husk.
• Defective Formula: Epidemics have occurred in infants fed soy-based formulas deficient in thiamine.
• Thiamine Antagonists: Consumption of foods containing thiaminases (e.g., fermented fish) or antagonists like tea and coffee by the mother or child.
• Cooking Practices: Repeated washing of rice and discarding cooking water results in significant vitamin loss.

Genetic Causes (Thiamine Dependency States)

• Thiamine-Responsive Megaloblastic Anemia (TRMA): Caused by variants in the SLC19A2 gene encoding a thiamine transporter.
• Biotin-Thiamine-Responsive Basal Ganglia Disease (BTBGD): Caused by variants in SLC19A3 gene.

Clinical Features of Infantile Beriberi

Infantile beriberi has a more subtle onset than adult forms but can progress rapidly. Symptoms often appear within the first 2–3 months of life.

General and Prodromal Symptoms

• Gastrointestinal: Anorexia, nausea, vomiting, and abdominal discomfort.
• Constitutional: Listlessness, fatigue, apathy, and irritability.
• Growth: Failure to thrive is a common early sign.

Cardiovascular Manifestations (Wet Beriberi)

• Presentation: This form is dominated by signs of congestive heart failure.
• Clinical Signs:
  • Cardiomegaly.
  • Tachycardia and dyspnea.
  • Cyanosis.
  • Peripheral edema may be present, though fluid accumulation is often due to cardiac dysfunction.
• Shoshin Beriberi (Fulminant Form):
  • A severe, acute presentation characterized by metabolic acidosis.
  • Presents with hypotension and cardiogenic shock.
  • Can lead to death within hours if untreated.

Neurological Manifestations (Dry Beriberi)

• Laryngeal Nerve Paralysis: A characteristic sign causing hoarseness or aphonia (loss of voice).
  • The infant may appear to be crying but produces no sound.
• Peripheral Neuritis:
  • Peripheral neuropathy is less common in infants than adults but may manifest as ptosis of the eyelids.
  • Muscle atrophy and loss of deep tendon reflexes.
  • Loss of vibration and position sense.
• Encephalopathy (Wernicke-like features):
  • Although classic Wernicke triad is rare in infants, severe deficiency (e.g., defective formula) can cause ophthalmoplegia, nystagmus, and lethargy.
  • Increased intracranial pressure, meningismus, and coma may develop in late stages.
  • Seizures may occur.

Genetic Syndromes Features

• TRMA (Rogers Syndrome): Characterized by the triad of megaloblastic anemia, diabetes mellitus, and sensorineural hearing loss.
• BTBGD: Presents with recurrent subacute encephalopathy (lethargy, dystonia, rigidity, dysphagia, seizures) often triggered by febrile illness.

Diagnosis

Clinical Diagnosis

• Diagnosis is often based on the clinical setting (dietary history) and compatible symptoms (unexplained cardiac failure or aphonia).
• A high index of suspicion is required as prompt treatment can be lifesaving.

Biochemical Tests

• Erythrocyte Transketolase Activity (ETKA): Low activity is a diagnostic criterion.
• Thiamine Pyrophosphate (TPP) Effect: An increase in ETKA activity by >14% after adding TPP indicates deficiency.
• Urinary Excretion: Measurement of thiamine or its metabolites (thiazole/pyrimidine) after a loading dose helps identify deficiency states.
• Lactate: Lactic acidosis may be present, particularly in acute fulminant forms or genetic defects like TPK1 deficiency.

Neuroimaging

• MRI: In infants, changes typically show bilateral symmetric hyperintensities in the basal ganglia (putamen, caudate) and frontal lobes.
• Lesions may also involve mammillary bodies, periaqueductal region, and thalami.

Management

Acute Treatment

• Route: Intravenous (IV) or Intramuscular (IM) administration is required for severe cases.
• Dosage: Children with cardiac failure, convulsions, or coma should receive 10–50 mg of thiamine daily.
• Duration: Parenteral therapy is recommended for the first week.
• Response:
  • Cardiac and neurologic symptoms (like apathy) typically improve dramatically within 24–48 hours.
  • Neurologic deficits (e.g., structural damage) resolve slowly and improvement may be incomplete.

Maintenance and Follow-up

• Oral Therapy: Following the initial parenteral course, oral thiamine should be continued at a dose of 3–5 mg/day for at least 6 weeks.
• Concurrent Deficiencies: Patients often have multiple B-complex deficiencies; a balanced diet or multivitamin supplementation is recommended.
• Dietary Modification:
  • Maternal diet improvement is crucial for breastfed infants.
  • Introduction of legumes, nuts, and enriched cereals.
  • Use of parboiled rice (steaming rice in husk retains vitamins) instead of polished rice.

Management of Genetic Thiamine Defects

• Thiamine-Responsive Megaloblastic Anemia (TRMA): Requires pharmacological doses of thiamine, typically 50–200 mg/day.
  • Anemia responds well; insulin requirements for diabetes may decrease.
• Biotin-Thiamine-Responsive Basal Ganglia Disease (BTBGD): Treated with a combination of:
  • Biotin: 5–10 mg/kg/day.
  • Thiamine: Up to 40 mg/kg/day.
  • Requires lifelong supplementation.

Prognosis and Complications

• Cardiovascular: Usually responds well to treatment.
• Neurological: Severe infantile deficiency can lead to permanent sequelae, including epilepsy, intellectual disability, and auditory/language problems in survivors.
• Sudden Death: Can occur in the fulminant cardiac form (Shoshin beriberi) if not recognized and treated immediately.