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Neurology 2002;59:1746-1749
© 2002 American Academy of Neurology

Biochemical markers predicting survival in peroxisome biogenesis disorders

J. Gootjes, MSc, P.A.W. Mooijer, BSc, C. Dekker, BSc, P.G. Barth, MD PhD, B.T. Poll-The, MD PhD, H.R. Waterham, PhD and R.J.A. Wanders, PhD

From the Laboratory Genetic Metabolic Diseases (J. Gootjes, P.A.W. Mooijer, and C. Dekker, and Drs. Waterham and Wanders) and the Department of Pediatrics/Emma Children’s Hospital (Drs. Barth and Poll-The), Academic Medical Center, University of Amsterdam, The Netherlands.

Address correspondence and reprint requests to Prof. Dr. Ronald J.A. Wanders, Lab. Genetic Metabolic Diseases (F0-224), Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands; e-mail: r.j.wanders{at}amc.uva.nl

Objective: To identify prognostic markers reflecting the extent of peroxisome dysfunction in primary skin fibroblasts from patients with peroxisome biogenesis disorders (PBD).

Background: PBD are a genetically heterogeneous group of disorders due to defects in at least 11 distinct genes. Zellweger syndrome is the prototype of this group of disorders, with neonatal adrenoleukodystrophy and infantile Refsum disease as milder variants. Common to these three disorders are liver disease, variable neurodevelopmental delay, retinopathy, and perceptive deafness. Because genotype-phenotype studies are complicated by the genetic heterogeneity among patients with PBD, the authors evaluated a series of biochemical markers as a measure of peroxisome dysfunction in skin fibroblasts.

Methods: Multiple peroxisomal functions including de novo plasmalogen synthesis, dihydroxyacetonephosphate acyltransferase (DHAPAT) activity, C26:0/C22:0 ratio, C26:0 and pristanic acid ß-oxidation, and phytanic acid {alpha}-oxidation were analyzed in fibroblasts from a series of patients with defined clinical phenotypes.

Results: A poor correlation with age at death was found for de novo plasmalogen synthesis, C26:0/C22:0 ratio, and phytanic acid {alpha}-oxidation. A fairly good correlation was found for pristanic acid ß-oxidation, but the best correlation was found for DHAPAT activity and C26:0 ß-oxidation. A mathematic combination of DHAPAT activity and C26:0 ß-oxidation showed an even better correlation.

Conclusions: DHAPAT activity and C26:0 ß-oxidation are the best markers in predicting life expectancy of patients with PBD. Combination of both markers gives an even better prediction. These results contribute to the management of patients with PBD.






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