Adrenomyeloneuropathy

Adrenomyeloneuropathy (AMN) is a form of X-linked adrenoleukodystrophy (X-ALD) caused by mutations in the ABCD1 gene. It is characterized by adult-onset spinal cord disease with possible adrenal involvement. AMN results from the accumulation of very long-chain fatty acids in the brain’s white matter and the adrenal glands due to impaired peroxisomal beta-oxidation.

Most individuals with AMN experience progressive stiffness and weakness of the legs (spastic paraparesis), gait disturbances, and selective loss of vibration and proprioception. Sensory neuropathy, bladder or bowel dysfunction, and sexual difficulties can occur. Adrenal insufficiency (Addison disease) is present in a substantial subset and can cause fatigue, weight loss, abdominal pain, low blood pressure, and hyperpigmentation.

Pathophysiology centers on the buildup of very long-chain fatty acids in plasma and tissues, leading to demyelination and axonal damage in the spinal cord and, less commonly, other CNS regions. Diagnosis is supported by biochemical testing showing elevated very long-chain fatty acids, especially increased C26:0 and an elevated C24:0/C22:0 ratio, and by identification of an ABCD1 gene mutation. MRI may reveal spinal cord and brain white-matter changes, though cerebral involvement is less common than in childhood forms.

There is no cure for AMN. Management focuses on symptom control and hormone replacement for adrenal insufficiency when present. This includes physical therapy, mobility aids, analgesia, and treatment of spasticity. Hematopoietic stem cell transplantation is not routinely used for AMN but is considered in cerebral ALD. Prognosis varies; male patients typically develop progressive neurological impairment, while female carriers may have milder symptoms.