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Stefan Schönberger, MD; Peter Roerig, PhD; Dominik T. Schneider, MD; Guido Reifenberger, MD; Ulrich Göbel, MD; Jutta Gärtner, MD

Arch Neurol. 2007;64(5):651-657. Published online March 12, 2007 (doi:10.1001/archneur.64.5.noc60105).

Background  X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder. It is caused by impaired function of ALD protein that results in accumulation of very long-chain fatty acids in tissues and body fluids. So far, hematopoietic stem cell transplantation (HSCT) constitutes the only curative approach able to prevent the progression of cerebral X-ALD. However, biological mechanisms of this beneficial approach are still unknown.

Objective  To describe the effect of HSCT in a family with various X-ALD disease forms by ALD mutation and protein expression analysis.

Design, Setting, and Patients  In a family with various X-ALD forms, an ALD mutation screening was performed. Two boys had cerebral X-ALD and underwent HSCT. One of them is alive and well without any further neurological deterioration, whereas his cousin died of transplantation-related complications at day 76. The postmortem specimens were analyzed by genotyping and immunohistochemical assays.

Results  All of the affected family members carry an as-yet-undescribed large ALD gene deletion (NC_000023:g.152512130-152520645del) resulting in a complete lack of ALD protein expression on immunofluorescence analysis. After engraftment, both patients who underwent HSCT showed complete chimerism in blood. Postmortem studies in 1 patient revealed both mutant and wild-type ALD sequences in each of 23 analyzed tissues, indicating mixed chimerism. Furthermore, immunohistochemical staining for ALD protein revealed no differences between patient and control tissues including blood cells, bone marrow, and glial cells as well as neurons.

Conclusion  To our knowledge, our analysis provides the first evidence for the stable development of a wild-type X-ALD genotype and peroxisomal ALD protein expression in a great variety of human tissues following HSCT.

Author Affiliations: Clinic for Pediatric Oncology, Hematology, and Immunology, University Children's Hospital (Drs Schönberger, Schneider, and Göbel) and Department of Neuropathology (Drs Roerig and Reifenberger), Heinrich-Heine-University, Düsseldorf, Germany; and Department of Pediatrics and Pediatric Neurology, University of Göttingen, Göttingen, Germany (Dr Gärtner).

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