PHENOTYPE OF PATIENTS WITH PEROXISOMAL DISORDERS SUBDIVIDED INTO 16 COMPLEMENTATION GROUPS

Objective: To use the technique of complementation analysis to help de fine genotype and classify patients with clinical manifestations consi stent with those of the disorders of peroxisome assembly, namely the Z ellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantil e Refsum disease (IRD), and rhizomelic chondrodysplasia punctata (RCDP ). Study design: Clinical findings, peroxisomal function, and compleme ntation groups were examined in 173 patients with the clinical manifes tations of these disorders. Results: In 37 patients (21%), peroxisome assembly was intact and isolated deficiencies of one of five peroxisom al enzymes involved in the beta-oxidation of fatty acids or plasmaloge n biosynthesis were demonstrated. Ten complementation groups were iden tified among 93 patients (54%) with impaired peroxisome assembly and o ne of three phenotypes (ZS, NALD, or IRD) without correlation between complementation group and phenotype. Forty-three patients (25%) had im paired peroxisome assembly associated with the RCDP phenotype and belo nged to a single complementation group, Of the 173 patients, 10 had un usually mild clinical manifestations, including survival to the fifth decade or deficits limited to congenital cataracts. Conclusions: At le ast 16 complementation groups, and hence genotypes, are associated wit h clinical manifestations of disorders of peroxisome assembly. The ran ge of phenotype is wide, and some patients have mild involvement.