Variant rhizomelic chondrodysplasia punctata (RCDP) with normal plasma phytanic acid: clinico-biochemical delineation of a subtype and complementation studies.

Rhizomelic chondrodysplasia calcificans punctata (RCDP) is an autosomal recessive peroxisomal disorder which affects phytanic acid oxidation and de novo biosynthesis of plasmalogens in liver and fibroblasts. Peroxisomal thiolase is present in its unprocessed precursor form (44 kDa). We studied a mentally retarded 9-year-old girl with cataracts and atypical bone dysplasia. Neurological findings were mild compared to classic RCDP. Plasma phytanic acid was normal. Results of de novo plasmalogen synthesis and phytanic acid oxidation studied in cultured skin fibroblasts were intermediate between normal controls and classic RCDP. Peroxisomal thiolase was present only as the unprocessed 44 kDa protein. Taken together these results suggest that we are dealing with a variant form of RCDP with clinical and biochemical abnormalities much milder as compared to classic RCDP. In order to establish the genetic relationship between our patient and classic RCDP patients complementation studies were carried out. Earlier studies had already shown that fibroblasts from all RCDP patients studied belong to a single complementation group. Fibroblasts from our patient could also be assigned to this complementation group suggesting that the phenotypic variability results from different mutations within the same gene.