X-Adrenoleukodystrophy

Introduction: X-adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder characterized by adrenal insufficiency and neurological manifestations. The disorder is caused by a defect in the ABCD1 gene, leading to inability to degrade very long chain fatty acids (VLCFA) and to their accumulation in tissues and fluids. The disorder is recessively inherited and X-linked with clinical manifestation predominantly in males. Clinical manifestation includes several phenotypes of X-ALD. The aim of the study was to review current knowledge on X-ALD and our options for laboratory, radiological and genetic diagnosis of the disorder and treatment approaches. Material and methods: Our study group included 11 patients, five with childhood cerebral form, one with the adolescent cerebral form, two with primary adrenal insufficiency, one with andrenomyeloneuropathy and two symptomatic females. All patients underwent VLCFA testing, brain MRI and DNA analysis of the ABCD1 gene. Results: Pathologically elevated VLCFA plasma levels were found in all patients. MRI revealed changes in white matter typically distributed in parietal-occipital areas in all but one patient. Mutation of the ABCD1 gene was confirmed in all patients. All male patients were treated with Lorenzo's oil. Two patients with cerebral form died within 2 years since the clinical onset of the disease. One patient was successfully transplanted (sibling transplantation of umbilical cord blood). Conclusion: The birth rate in Slovakia is about 60 thousand children per year, and the incidence of the X-ALD is from 1: 16,800 to 1: 42,000. Therefore, we presume that there will be one to three new cases each year. It is important to recognize the disorder from its typical clinical manifestationa. Due to the close relationship between the disorder and endocrinopathies, education of endocrinologists is considered important, in order to increase their ability to identify possible cases without neurological deficit. Cerebral forms of the disease in their early stages can be succesfully treated with bone marrow or umbilical cord blood transplantation.