What is distinctive about adult-onset adrenoleukodystrophy?

Distinctive features of adult-onset adrenoleukodystrophy (ALD)

- Age of onset: Adrenoleukodystrophy (ALD) can affect individuals at different ages, but adult-onset ALD typically presents in individuals between the ages of 21-40.

- Slower progression: Compared to childhood ALD, adult-onset ALD tends to progress more slowly. The neurological symptoms may develop gradually over several years or even decades.

- Predominant neurological symptoms: Adult-onset ALD primarily affects the nervous system. Common neurological symptoms in adult-onset ALD include:

- Cognitive difficulties, such as memory impairment, impaired executive functioning, and decreased intellectual abilities

- Behavioral changes, including irritability, social withdrawal, and apathy

- Progressive spastic paraparesis, leading to weakness and stiffness in the legs

- Speech difficulties, such as dysarthria (difficulty speaking)

- Vision problems, such as optic neuritis (inflammation of the optic nerve)

- Hearing loss

- Seizures

- Adrenal insufficiency: Adrenal insufficiency is a less common but potentially serious complication in adult-onset ALD. It occurs due to the involvement of the adrenal glands, which produce hormones essential for various bodily functions. Symptoms of adrenal insufficiency may include fatigue, weight loss, gastrointestinal problems, and low blood pressure.

- Magnetic resonance imaging (MRI) findings: MRI scans of the brain in adult-onset ALD typically show abnormalities in the white matter, particularly in the frontal and parietal regions. These changes may appear as areas of increased signal intensity on T2-weighted or FLAIR MRI sequences.

- Genetic features: Adult-onset ALD is caused by mutations in the ABCD1 gene, which encodes a protein involved in the transport of very long-chain fatty acids (VLCFAs) across the cell membrane. These mutations lead to the accumulation of VLCFAs in the brain and other tissues, causing cellular damage and neurological dysfunction.

- Variable presentation: Adult-onset ALD exhibits a spectrum of clinical presentations. Some individuals may experience a relatively mild course with gradual progression of symptoms, while others may have a more rapid decline and develop severe neurological impairments.