Adrenomyeloneuropathy

Adrenomyeloneuropathy (AMN) is a form of X-linked adrenoleukodystrophy (X-ALD) caused by mutations in the ABCD1 gene, which encodes a peroxisomal membrane transporter protein involved in the breakdown of very long-chain fatty acids (VLCFAs). AMN is considered the adult-onset form of X-ALD and primarily affects the spinal cord and peripheral nerves, leading to progressive myelopathy and peripheral neuropathy. The accumulation of VLCFAs in tissues, particularly in the nervous system and adrenal glands, drives the disease process. The hallmark symptoms of AMN include progressive stiffness and weakness in the legs (spastic paraparesis), sensory disturbances in the lower extremities, bladder and bowel dysfunction, and sexual dysfunction. Symptoms typically begin in early adulthood, usually between the ages of 20 and 40. Many affected males also develop adrenal insufficiency (Addison disease), which may precede or accompany the neurological symptoms. Approximately 20% of men with AMN may eventually develop cerebral demyelination, which can lead to more rapid cognitive and neurological decline. Female carriers of ABCD1 mutations can also develop a milder myelopathy, often later in life, though they rarely develop adrenal insufficiency or cerebral involvement. There is currently no cure for AMN. Treatment is primarily supportive and symptomatic, including physical therapy, antispasticity medications, management of bladder dysfunction, and hormone replacement therapy for adrenal insufficiency. Lorenzo's oil and dietary VLCFA restriction have not been shown to alter the neurological progression in AMN. Hematopoietic stem cell transplantation (HSCT) and gene therapy (such as elivaldogene autotemcel) have shown benefit in the cerebral form of ALD but are not standard treatments for isolated AMN. Regular monitoring with brain MRI is recommended to detect early cerebral involvement. Elevated plasma VLCFA levels are the key diagnostic biomarker.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Adrenomyeloneuropathy