Peroxisome Disorders and Cutaneous Manifestations

J.-H. Saurat, Department of Dermatology, University Hospital Geneva, CH-1211 Geneva 14 (Switzerland) Beside complex structures such as endoplasmic reticu-lum or mitochondria that electron microscopy reveals in human cells, there are organelles bounded by a single membrane; some of these vesicles contain hydrogen-peroxide-generating enzymes and were therefore called ‘peroxisomes’ to reflect their role in peroxide metabolism. It was later found that enzymes catalyzing the ß-oxidation of fatty acids were located not only in mitochondria but also in per-oxisomes; in fact the most important metabolic role of the peroxisome seems to be shortening of very-longchain fatty acids ( > 22 carbon atoms) and oxidizing diand trihydroxy-coprostanic acids and pristanic acid, a metabolite of phyta-nic acid [1]. Thus peroxisomes contain enzymatic activities for ß-oxidation of fatty acids that are distinct from the mito-chondrial pathway. Peroxisomes are present in almost all mammalian cells (except erythrocytes) including keratinocytes [2]. Several inborn defects of peroxisomal function have been identified: Zellweger syndrome [3], adrenoleukodys-trophy (ALD) [4], rhizomelic chondrodysplasia punctata [5], CHILD syndrome [6], hyperpiperolic acidemia and infantile Refsum’s disease [7]. Of these, Refsum’s disease [8], as well as rhizomelic chondrodysplasia punctata [5] and CHILD syndrome [6] are associated with skin alterations, an ichthyotic-like condition [9]. In this issue of Dermatology, Papini et al. [8] report the dermatological findings in a patient with X-linked ALD and the metabolic disturbances detectable in the skin surface lipids. X-linked ALD is a rare peroxisomal disorder, affecting 1/20,000 males. The disease is characterized by an accumulation of very-long-chain fatty acids because of impaired shortening in peroxisomes. Diagnosis of X-linked ALD is based on the demonstration of high serum levels of very-long-chain fatty acids. Clinical manifestations are central nervous system demyelination and adrenal insufficiency. However, striking variation of the clinical phenotype exists. The gene locus for ALD has been mapped to the terminal segment of the long arm of the X chromosome (Xq28) [10]. The gene responsible for the production of the ALD protein has been found recently by Mosser et al. [4]. It encodes a protein with homology to a 70-kD peroxisomal membrane protein which is involved in peroxisome biogenesis. The sequence of ALD protein and 70-kD peroxisomal membrane protein is very similar but not identical. Both proteins belong to the ATP-binding transporter protein superfamily. Gartner et al. [11] localized the human peroxisomal membrane protein 70-kD gene, which has a documented role in Zellweger syndrome, to chromosome 1. Aubourg et al. [12] reported reversal of neurologic and neuroradiologic features in a boy with ALD by bone marrow transplantation from his fraternal twin brother. Rizzo et al. [13] concluded from their study that dietary erucic acid therapy is effective in ALD.