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SynopsisAdrenoleukodystrophy is a rare X-linked disorder caused by mutations in the ABCD1 gene, which encodes a peroxisomal membrane protein necessary for breakdown of very long-chain fatty acids (VLCFA). This leads to accumulation of VLCFA in the brain, adrenal glands, and testes.
Adrenoleukodystrophy has multiple phenotypes with variable presentations in males versus females. The main types are as follows:
- The childhood cerebral type has onset between ages 4 and 10 years and is characterized by progressive behavioral and cognitive changes, vision loss, dysphagia, seizures, and adrenal insufficiency. Deterioration is often rapid, with death often occurring between 6 months to 10 years after diagnosis.
- The adrenomyeloneuropathy type occurs between the second and fourth decade and is marked by progressive spastic paraparesis, spinal cord dysfunction, adrenal insufficiency, urinary and genital disorders, and altered cognition and behavior. This type may lead to disability, and severe cases may cause early death.
- The "Addison disease only" type has onset before age 10 and is characterized by primary adrenal insufficiency without apparent neurologic involvement.
Female carriers often develop adult-onset myeloneuropathy presenting with increased reflexes and distal sensory changes in lower extremities but rarely have cerebral involvement.
E71.529 – X-linked adrenoleukodystrophy, unspecified type
65389002 – Adrenoleukodystrophy
Differential Diagnosis & Pitfalls
- Metachromatic leukodystrophy
- Krabbe disease
- Alexander disease
- Canavan disease
- Neuronal ceroid lipofuscinoses
- Pelizaeus-Merzbacher disease
- Mitochondrial disorders, eg, Leigh syndrome
- Encephalitis, eg, subacute sclerosing panencephalitis
- Brain tumor (eg, glioblastoma multiforme, oligodendroglioma, ependymoma, medulloblastoma)
- Spinal cord tumor (eg, meningioma, medulloblastoma, metastases, ependymoma)
- Hereditary spastic paraparesis
- Vitamin B12 deficiency
- Multiple sclerosis
- Epilepsy (see seizure)