Five men with arresting and relapsing cerebral adrenoleukodystrophy.

Area of Science:

• Neurology
• Genetics
• Peroxisomal Disorders

Background:

• X-linked adrenoleukodystrophy (ALD) is a common genetic peroxisomal disorder affecting approximately 1:15,000 males.
• Two-thirds of males with ALD develop the cerebral phenotype (cALD), characterized by progressive inflammatory demyelinating lesions.
• Early hematopoietic stem-cell transplantation can halt cALD, but effectiveness diminishes with disease progression.

Purpose of the Study:

• To describe a previously undocumented variant of cerebral adrenoleukodystrophy (cALD) characterized by lesion arrest and subsequent relapse.
• To document the clinical and radiographic features of this novel arresting-relapsing cALD phenotype.

Main Methods:

• Review and summarization of clinical and radiographic data from cALD patients exhibiting episodic deteriorations.
• Longitudinal follow-up of patients with spontaneously arrested cALD lesions.

Main Results:

• Five unrelated men with cALD exhibited spontaneously arrested lesions that later showed renewed clinical and radiographic progression.
• In three of five patients, disease progression occurred when they were too debilitated for transplantation.
• One patient experienced lesion reactivation followed by another spontaneous arrest.

Conclusions:

• The findings underscore the importance of continuous clinical and radiographic surveillance in adult males with ALD.
• Vigilance is crucial for detecting new or reactivated cALD lesions to enable timely treatment evaluation.
• This study identifies a novel arresting-relapsing variant of cALD, necessitating adapted monitoring strategies.