Clinical Variation and Neuroimaging Patterns in Monozygotic Twins With Arrested X-Linked Adrenoleukodystrophy: A Case...

Area of Science:

• Neurology
• Genetics
• Peroxisomal Disorders

Background:

• X-linked adrenoleukodystrophy (ALD) is a genetic disorder characterized by very long-chain fatty acid accumulation in neural and adrenal tissues.
• ALD affects males and can lead to severe neurological impairment and adrenal insufficiency.

Observation:

• This report details 23-year-old monozygotic twins presenting with diverse neurological symptoms of ALD, including gait disturbance, muscle stiffness, and incontinence.
• Neurological examination revealed spastic gait and proximal lower extremity weakness, with symptom severity differing between the twins.
• Brain MRI showed T2 hyperintensity in the splenium of the corpus callosum, and spine MRI indicated thoracic spinal cord atrophy in both subjects.

Findings:

• Genetic testing confirmed a pathogenic variant in the ABCD1 gene in both twins.
• Despite identical genetics and similar initial MRI findings, the twins exhibited persistent differences in clinical symptom severity.
• Elevated hexacosanoic acid and primary adrenal insufficiency were noted in both individuals.

Implications:

• The observed clinical variability in monozygotic twins with ALD suggests that non-genomic factors play a significant role in disease pathogenesis.
• This case underscores the complexity of ALD, where identical mutations can lead to disparate clinical outcomes.
• Further research into epigenetic and environmental influences is warranted to understand ALD's diverse presentations.