Clinical scenario: Regression of milestones | Impaired sense of vibration | Hyperintensities on MRI brain
A 5-year-old girl is brought with a 9-month history of progressive gait difficulty and frequent falls. She was previously developmentally normal but has gradually become unable to climb stairs and has started slurring her speech. Her parents also report declining school performance and increasing emotional lability. Examination reveals distal muscle weakness, absent ankle and knee reflexes, impaired vibration sense, bilateral extensor plantar responses, and an ataxic gait. Brain MRI demonstrates symmetrical periventricular white matter hyperintensities with a tigroid appearance.
Which of the following is the most likely diagnosis?
A. X-linked adrenoleukodystrophy
B. Krabbe disease
C. Metachromatic leukodystrophy
D. Pelizaeus-Merzbacher disease
E. Friedreich ataxia
Correct answer & Explanation:
Correct Answer: C. Metachromatic leukodystrophy
Explanation:
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder caused by arylsulfatase A deficiency, resulting in accumulation of sulfatides in the central and peripheral nervous systems.
The characteristic clinical features include:
- Normal early development followed by regression
- Progressive gait disturbance and frequent falls
- Cognitive decline and behavioral changes
- Dysarthria
- Peripheral neuropathy causing absent deep tendon reflexes
- Progressive spasticity leading to extensor plantar responses
- MRI showing tigroid (leopard-skin) demyelination
The coexistence of upper motor neuron signs (Babinski sign) with lower motor neuron signs (absent reflexes due to peripheral neuropathy) is highly suggestive of MLD.
Why the Other Options Are Incorrect
A. X-linked adrenoleukodystrophy
- Usually affects boys.
- Hyperreflexia is common, but peripheral neuropathy with absent reflexes is less prominent.
- Hyperpigmentation from adrenal insufficiency is an important clue.
B. Krabbe disease
- Typically presents in infancy with irritability, hypertonia, feeding difficulty, and optic atrophy.
D. Pelizaeus-Merzbacher disease
- Presents in infancy with nystagmus, hypotonia, and delayed milestones rather than peripheral neuropathy.
E. Friedreich ataxia
- Causes ataxia and absent reflexes but MRI does not show diffuse leukodystrophy, and cognitive decline is uncommon.
High-Yield Pearls
- Enzyme deficiency: Arylsulfatase A
- Stored substrate: Sulfatides
- Inheritance: Autosomal recessive
- Peripheral neuropathy is a hallmark feature.
- MRI classically demonstrates a tigroid (leopard-skin) pattern of demyelination.
- Nerve conduction studies show markedly slowed conduction velocities due to demyelination.
- Diagnosis is confirmed by low arylsulfatase A enzyme activity and elevated urinary sulfatides.
Exam Pearl
A child with:
- Progressive frequent falls
- Cognitive decline
- Absent tendon reflexes
- Extensor plantar responses
- Tigroid MRI pattern
→ Think Metachromatic Leukodystrophy (MLD).
