Inherited neurometabolic disorders are individually rare and have many causes. Many are progressive disorders with treatment options limited to symptomatic care. X-linked adrenoleukodystrophy (ALD) is a rare disorder first described almost 100 years ago. As a result of intense basic science and clinical research, remarkable progress has been made in elucidating the biochemical irregularities, molecular genetics, diagnostic testing, and pathogenesis of this disorder. In recent years, extraordinary progress has also been made in developing effective treatments, and ALD serves as an excellent model for the treatment of neurometabolic diseases. It is a progressive disorder characterized by Addison disease, childhood dementia, and neurologic deterioration to a vegetative state. A key discovery was the identification of lipid inclusions consisting of cholesterol esters and an excess of very long-chain fatty acids (VLCFAs) in adrenal cells.1 This finding led to the development of specific assays for diagnosis, and it localized the subcellular irregularity to peroxisomes. In addition, the range of symptoms secondary to elevated VLCFAs became clearly defined. X-linked ALD is a complex disease with multiple phenotypic variations. Each phenotype has it own natural history and, thus, different treatment regimens. Current treatment includes hematopoietic stem cell transplantation (HSCT) to stabilize neurologic progression, steroid therapy for adrenal insufficiency, and symptomatic treatments. The article by Moser et al2 in this issue may establish new standards for the treatment of this degenerative disorder. They studied the effects of Lorenzo’s oil (LO) therapy in asymptomatic patients over a 13-year period and showed that a reduction of serum VLCFA correlates with a reduced risk of developing abnormalities visible by magnetic resonance imaging (MRI).
Ferri R, Chance PF. Lorenzo’s Oil: Advances in the Treatment of Neurometabolic Disorders. Arch Neurol. 2005;62(7):1045-1046. doi:10.1001/archneur.62.7.1045