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Thiamine Deficiency

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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.

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