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Adrenomyeloneuropathy (AMN) is the adult-onset phenotype of X-linked adrenoleukodystrophy (X-ALD)—a peroxisomal disorder caused by mutations in the ABCD1 gene.
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It is the most common variant seen in males and is characterized by progressive spinal cord and peripheral nerve involvement.
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Peroxisomal membrane protein defect, leading to abnormal myelin incorporation of fatty acids
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| Feature | Details |
|---|---|
| Inheritance | X-linked recessive |
| Gene mutation | ABCD1 on Xq28 |
| Pathophysiology | Defective peroxisomal β-oxidation → accumulation of very long chain fatty acids (VLCFA) |
| Target tissues | Spinal cord, peripheral nerves, adrenal cortex, and testes |
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Often begins with behavioral problems and gait disturbance, followed by visuospatial deficits and adrenal insufficiency
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| System | Presentation |
|---|---|
| Neurological | Slowly progressive spastic paraparesis, sensory ataxia, bladder dysfunction |
| Peripheral nerves | Distal symmetric sensorimotor neuropathy |
| Adrenal | Primary adrenal insufficiency (Addison’s disease), often precedes neurologic symptoms |
| Onset | Typically in the 2nd–4th decade (adult-onset form) |
| Sex affected | Males (X-linked), but female carriers may also show milder myelopathy |
MRI Findings
| Domain | Imaging features |
|---|---|
| Spinal Cord | |
| Myelopathy) | MRI changes in spinal cord correlate with the degree of spasticity and disability: |
| • Diffuse symmetric T2 hyperintensity in lateral and posterior columns of the thoracic spinal cord | |
| • Spinal cord atrophy, especially in chronic stages | |
| • No significant enhancement | |
| Brain | May show normal brain MRI in early AMN. In later stages it can overlap with cerebral ALD but is less severe: |
| • Parieto-occipital white matter changes | |
| • Corpus callosum involvement | |
| • Symmetric T2 hyperintensities in periventricular white matter |
Neuroimaging spectrum in X-ALD (A–E) and AMN (F–J). MRI brain T2 axial sequences (A, B) in the frontal/reverse variant of X-ALD reveal confluent subcortical, deep, and periventricular white matter hyperintensity involving frontal lobes in a symmetric distribution with associated volume loss. Note similar changes of less severe magnitude in the parieto-occipital regions and involvement of corpus callosum. T1 post-contrast image (C) shows subtle enhancement along the periphery of the involved frontal white matter. MRI T2 axial and T1 post-contrast (D and E) in classic X-ALD reveals confluent white matter hyperintensity involving the splenium of the corpus callosum and adjacent parieto-occipital white matter along with the contrast enhancement of the advancing margins. MRI T2W sequences in an individual with adrenomyeloneuropathy: axial (F, G, H) and coronal (I) sequences with signal changes along the corticospinal tract in the brain stem and posterior limb of the internal capsule. Note the signal changes stopping at the posterior limb of the internal capsule and not extending to the cortex. Superior extension of corticospinal tract signal changes beyond the posterior limb of the internal capsule represents the cerebral involvement of ALD; T2 sagittal MRI of the spine reveals marked diffuse cervical and thoracic cord thinning.
Muthusamy K, Sivadasan A, Dixon L, Sudhakar S, Thomas M, Danda S, Wszolek ZK, Wierenga K, Dhamija R and Gavrilova R (2023) Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions. Front. Neurol. 14:1219324. doi: 10.3389/fneur.2023.1219324
| Condition | Key Differences |
|---|---|
| Hereditary spastic paraparesis | No adrenal involvement, family history may help |
| Primary lateral sclerosis | No sensory involvement or adrenal dysfunction |
| Multiple sclerosis | Disseminated lesions with relapsing-remitting course |
| Vitamin B12 deficiency | Megaloblastic anemia, subacute combined degeneration, positive serum B12 |