ALD

Adrenoleukodystrophy (ALD) is a genetic disorder that affects the nervous system and the adrenal glands. It is characterized by the accumulation of very long-chain fatty acids (VLCFAs) in tissues throughout the body, including the brain and the adrenal cortex, due to a defect in the peroxisomal VLCFA transporter protein. This accumulation leads to progressive demyelination, affecting the neurons in the brain and impairing adrenal gland function. ALD is a X-linked recessive disorder, meaning it primarily affects males, though female carriers can have milder symptoms.

The condition encompasses several phenotypic forms, including childhood cerebral ALD, adrenomyeloneuropathy (AMN), and Addison-only phenotype. Childhood cerebral ALD is the most severe form, typically presenting between the ages of 4 and 10 years old, with symptoms such as behavioral changes, vision loss, ataxia, and progressive dementia. Adrenomyeloneuropathy presents in adulthood with progressive spastic paraparesis, peripheral neuropathy, and adrenal insufficiency. The Addison-only phenotype is characterized by primary adrenal insufficiency without significant neurological involvement.

Diagnosis of ALD involves the measurement of VLCFA levels in the plasma, which are elevated in affected individuals. Genetic testing can confirm the diagnosis by identifying mutations in the ABCD1 gene, which encodes the ALD protein responsible for the transport of VLCFAs into peroxisomes for degradation.

Treatment options for ALD are limited and focus on managing symptoms and slowing disease progression. Adrenal insufficiency is treated with corticosteroid replacement therapy. In cases of childhood cerebral ALD, hematopoietic stem cell transplantation (HSCT) may be considered if performed at an early stage of the disease, as it can slow or halt the progression of demyelination. Lorenzo's Oil, a dietary treatment that involves a mixture of glyceryl trioleate and glyceryl trierucate, has been shown to lower VLCFA levels in the plasma but its effectiveness in altering the course of the disease is still under investigation.

Research into new treatments, including gene therapy and new medications to manage symptoms and potentially slow disease progression, is ongoing. Gene therapy, in particular, has shown promise in early clinical trials by introducing a functional copy of the ABCD1 gene into the patient's own hematopoietic stem cells.