COMPLEMENTATION ANALYSIS IN PATIENTS WITH THE CLINICAL PHENOTYPE OF AGENERALIZED PEROXISOMAL DISORDER

The generalised peroxisomal disorders (GPDs) Zellweger syndrome (ZS), neonatal adrenoleucodystrophy (NALD), and infantile Refsum's disease ( IRD) are autosomal recessive disorders associated with a failure to as semble mature peroxisomes. We confirmed the diagnosis of a GPD in eigh t ZS and four IRD patients (GPD1 to GPD12) biochemically by measuring very long chain fatty acids, plasmalogen biosynthesis, and catalase so lubility in skin fibroblasts. One further patient (BOX-1) had the clin ical phenotype of ZS, but biochemical investigations indicated an isol ated deficiency of peroxisomal beta oxidation. To date a total of 10 c omplementation groups (CGs) for the GPDs and three further CGs for iso lated beta oxidation deficiencies have been identified. Most GPD patie nts have been shown to belong to CG-1 (Baltimore classification); amon g the rarer groups, CG-4 and CG-8 predominate. We performed somatic ce ll hybridisation experiments on strains GPD-1 to GPD-12 using plasmalo gen biosynthesis as a marker for correction and found that six ZS and three IRD patients, eight of whom were of UK origin, belonged to CG-1. Strain GPD-11, a patient of UK origin with an unusual biochemical phe notype, belonged to CG-8. Strains GPD-10 and GPD-12 were derived from ZS patients of Arabian and Pakistani origin and belonged to the rarer CGs 2 and 7, respectively. Furthermore, complementation analysis using beta oxidation as a marker showed that BOX-1 had an isolated deficien cy of the bifunctional protein.