Adrenoleukodystrophy

Adrenoleukodystrophy is a rare genetic disorder that affects the nervous system and the adrenal glands. It causes a buildup of very long-chain fatty acids (VLCFAs) in the body, which damages the protective covering of nerve cells called the myelin sheath. This damage leads to problems with movement, coordination, and behavior. The disease mainly affects boys and men because it is linked to the X chromosome. Symptoms often start in childhood but can appear later in life. Over time, the condition can cause severe disability due to progressive nerve damage and adrenal gland failure.

Adrenoleukodystrophy (ALD) is an X-linked recessive disorder caused by mutations in the ABCD1 gene, leading to defective peroxisomal beta-oxidation of very long-chain fatty acids (VLCFAs). This results in accumulation of VLCFAs in the central nervous system, adrenal cortex, and testes, causing progressive demyelination and adrenal insufficiency. The core pathology involves inflammatory demyelination of cerebral white matter and adrenal gland dysfunction. Clinically, ALD presents with neurologic decline, including cognitive impairment, motor dysfunction, and adrenal insufficiency symptoms such as fatigue and hyperpigmentation. The disease has variable phenotypes, including childhood cerebral ALD, adrenomyeloneuropathy, and Addison-only presentations. Early diagnosis is critical due to the potential for rapid progression and severe neurologic disability.