Adrenoleukodystrophy: heterogeneity in two brothers

Area of Science:

• Neurology
• Genetics
• Biochemistry

Background:

• Adrenoleukodystrophy (ALD) is an X-linked metabolic disorder characterized by very long-chain fatty acid accumulation.
• It affects the adrenal glands, testes, and white matter of the central nervous system.
• ALD exhibits significant phenotypic heterogeneity, complicating diagnosis and classification.

Observation:

• A patient presenting with hypoadrenalism and rapidly progressive pseudobulbar palsy was diagnosed with adult-onset ALD.
• This diagnosis prompted the investigation of his brother, who had a history of spastic paraparesis.
• Both siblings' conditions were biochemically confirmed as manifestations of ALD.

Findings:

• The study confirms that adult-onset adrenoleukodystrophy can manifest as severe neurological deficits, including pseudobulbar palsy and spastic paraparesis.
• Biochemical analysis validated the diagnosis in both affected individuals.
• The cases illustrate the wide spectrum of clinical presentations and variable expressivity of ALD.

Implications:

• Recognizing the phenotypic heterogeneity of ALD is crucial for timely diagnosis and management.
• Biochemical testing is essential for confirming ALD, especially in cases with atypical neurological presentations.
• Standardized nomenclature and diagnostic criteria are needed to address the complexities of X-linked disorders like ALD.