Clinical scenario: Declining school performance| Frequent falls | Hyperpigmentation
An 8-year-old boy is brought with progressive decline in school performance over the past 8 months. His teacher reports increasing inattentiveness and difficulty reading and writing despite previously being an excellent student. His parents have also noticed frequent falls while running, increasing clumsiness, and recent behavioral changes. On examination, he has spastic paraparesis, brisk deep tendon reflexes, extensor plantar responses, and generalized hyperpigmentation involving the knuckles, elbows, and buccal mucosa. His visual acuity is reduced, and fundoscopy is normal.
Which of the following is the most likely diagnosis?
A. Metachromatic leukodystrophy
B. Friedreich ataxia
C. X-linked adrenoleukodystrophy
D. Pelizaeus-Merzbacher disease
E. Krabbe disease
Correct answer & Explanation:
Correct Answer: C. X-linked adrenoleukodystrophy
Explanation:
X-linked adrenoleukodystrophy (ALD) is caused by mutations in the ABCD1 gene, resulting in defective peroxisomal β-oxidation and accumulation of very-long-chain fatty acids (VLCFAs) in the brain, adrenal cortex, and testes.
The hallmark features in the childhood cerebral form include:
- Previously normal child
- Progressive decline in school performance (often the earliest symptom)
- Behavioral and personality changes
- Visual and hearing impairment
- Progressive spasticity and frequent falls
- Hyperreflexia and extensor plantar responses
- Hyperpigmentation due to primary adrenal insufficiency (Addison disease)
The coexistence of neurological deterioration and hyperpigmentation is a classic examination clue for ALD.
Why the Other Options Are Incorrect
A. Metachromatic leukodystrophy
- Progressive motor and cognitive decline but adrenal insufficiency and hyperpigmentation are absent.
B. Friedreich ataxia
- Presents with gait ataxia and absent reflexes rather than spasticity.
- No adrenal involvement.
D. Pelizaeus-Merzbacher disease
- Characterized by nystagmus, hypotonia, and hypomyelination beginning in infancy.
- Hyperpigmentation is not a feature.
E. Krabbe disease
- Usually presents in infancy with irritability, developmental regression, and optic atrophy rather than isolated school decline.
- No adrenal insufficiency.
High-Yield Pearls
- Declining school performance is often the earliest manifestation of childhood cerebral ALD.
- Hyperpigmentation is a vital clue indicating associated primary adrenal insufficiency.
- Neurological signs include:
- Spastic paraparesis
- Hyperreflexia
- Frequent falls
- Visual and auditory impairment
- MRI typically shows symmetrical parieto-occipital white matter demyelination with gadolinium enhancement at the advancing edge.
- Diagnosis is confirmed by elevated plasma very-long-chain fatty acids (especially C26:0) and ABCD1 gene testing.
- Early hematopoietic stem cell transplantation may halt disease progression if performed before advanced neurological deficits develop.
Exam Pearl
A school-aged boy with:
- Progressive poor school performance
- Behavioral changes
- Frequent falls
- Spasticity
- Hyperpigmentation
→ Think X-linked adrenoleukodystrophy until proven otherwise.
