Follow-up of 89 Asymptomatic Patients With Adrenoleukodystrophy Treated With Lorenzo’s Oil

Abstract

X-linked adrenoleukodystrophy (ALD) is due to a defect in the gene ABCD1, which codes for a peroxisomal membrane protein¹ and is associated with the accumulation of saturated very long-chain fatty acids (VLCFAs) such as hexacosanoic acid (C26:0).² There is considerable evidence that this accumulation contributes to ALD pathogenesis.^3-6 There are 4 major phenotypes of ALD: (1) the rapidly progressive cerebral ALD (CERALD) phenotypes, which are most common in childhood and are associated with inflammatory demyelination⁷; (2) adrenomyeloneuropathy (AMN), a slowly progressive noninflammatory distal axonopathy that involves the spinal cord long tracts⁸; (3) the Addison-only phenotype of primary adrenocortical insufficiency without demonstrable neurological deficit; and (4) asymptomatic status without clinically evident neurological or endocrine abnormality. Multiple phenotypes often co-occur in a family. The nature of the mutation does not correlate with the phenotype. Modifier genes that influence phenotypic expression are suspected but have not been defined. Demonstration of increased plasma VLCFA levels is the most frequently used diagnostic assay.⁹ Adrenal hormone replacement and hematopoietic stem cell transplantation (HSCT) are the currently accepted therapies. The latter is of long-term benefit for boys and adolescents in the early stages of CERALD, but it is not recommended for the asymptomatic, Addison-only, or AMN phenotypes or for those with advanced CERALD.¹⁰ We present the first follow-up study of asymptomatic patients with ALD and examine whether administration of 4:1 glyceryl trioleate–glyceryl trierucate (Lorenzo’s oil [LO]) to asymptomatic patients with ALD can reduce the risk of developing neurological abnormalities.