Infantile Tremor Syndrome

1. Introduction and Definition

• Definition: A clinical syndrome characterized by the triad of tremors, mental regression/developmental delay, and skin pigmentation in a plump, anemic infant.
• Historical Context: First described in India (Dikshit, 1957). Also known as "Pre-kwashiorkor" or "Nutritional Tremor Syndrome."
• Current Consensus: It is primarily a manifestation of severe Vitamin B12 deficiency.

2. Epidemiology

• Geography: Predominantly seen in the Indian subcontinent (India, Pakistan, Nepal) and Southeast Asia.
• Age: 6 months to 18 months (Peak: 1 year).
• Sex: Male slight preponderance.
• Socioeconomic: Lower socioeconomic strata, though seen in middle class with strict vegetarianism.
• Maternal Factors: Exclusively breastfed infants of vegetarian mothers or mothers with pernicious anemia/malabsorption.

3. Etiopathogenesis

• Primary Cause: Vitamin B12 (Cobalamin) Deficiency.
  • Maternal B12 stores are low (vegetarian diet) $\to$ Low B12 in breast milk $\to$ Infant depletion.
• Why Tremors?
  • B12 is essential for myelin synthesis. Deficiency leads to demyelination of basal ganglia and cortical pathways.
  • Accumulation of Methylmalonic Acid (neurotoxic).
• Other Factors (Contributory):
  • Magnesium deficiency.
  • Zinc deficiency.
  • Iron deficiency (co-existing).
  • Older theories of viral encephalitis are largely discarded.

4. Clinical Features

The disease typically evolves in stages:

A. Prodromal Phase (Pre-Tremor)

• Duration: 1–2 months before tremors.
• Behavior: Apathy, lethargy, irritability.
• Cry: Characteristic "Bleating Goat Cry" (weak, hoarse, monotonous).
• Regression: Loss of previously acquired milestones (e.g., inability to sit or hold head).
• Appearance: Infant appears plump/chubby ("Flabby infant"), often mistaken as healthy by parents.

B. Tremor Phase

• Onset: Sudden or subacute, often precipitated by an acute illness (fever/diarrhea).
• Characteristics of Tremor:
  • Type: Coarse, rhythmic, rapid.
  • Distribution: Distal parts of limbs ("Kite-flying" or "Polishing" movements). Also involves head (titubation), tongue, and eyelids.
  • State: Present at rest, aggravated by stimulation/handling, disappears during sleep.
• Neurology: Hypotonia (proximal) with hyperreflexia (distal); ankle clonus may be present.

C. Cutaneous Changes (Hallmark)

• Hyperpigmentation:
  • Knuckles, dorsum of hands/feet, elbows, knees, buttocks.
  • "Infantile Acropigmentation": Peripheral darkening.
• Hair: Sparse, light-colored, brittle (Hypopigmentation/Flag sign).
• Pallor: Severe waxy pallor due to anemia.

5. Investigations

6. Differential Diagnosis

7. Management

A. Specific Therapy (Vitamin B12)

• Parenteral: Inj. Vitamin B12 (Cyanocobalamin/Hydroxocobalamin).
  • Regimen: 1000 mcg IM daily for 3–7 days, then weekly for 4 weeks, then monthly.
• Response:
  • Tremors often transiently worsen initially during treatment before subsiding.
  • Tremors usually resolve within 1–2 weeks.
  • Pigmentation clears in 4–6 weeks.
  • Neurodevelopment recovery takes months.

B. Symptomatic Treatment for Tremors

• First Line: Propranolol (Beta-blocker) 1–2 mg/kg/day in divided doses.
• Second Line: Carbamazepine or Phenytoin (rarely needed).
• Sedation: Chloral hydrate or Triclofos if sleep is disturbed.

C. Nutritional Rehabilitation

• Iron & Folic Acid: Supplementation required as rapid hematopoiesis depletes iron stores.
• Diet: Introduction of complementary feeds (weaning).
• Maternal Treatment: Treat mother for B12 deficiency/Pernicious anemia.

8. Prognosis

• Short-term: Excellent. Tremors and anemia resolve completely.
• Long-term:
  • Cognitive: Studies suggest mild to moderate cognitive deficits (lower IQ) persist in older children compared to controls, despite physical recovery.
  • Physical: Catch-up growth is usually good.