Pseudoachondroplasia

Abstract

Cartilage from patients with pseudoachondroplasia is characterized by unique inclusions in the cisternae of the endoplasmic reticulum and proteoglycan abnormalities have been suggested in this form of dwarfism. To elucidate the nature of the proteoglycan defect, we determined the amount of the individual glycosaminoglycans present in iliac-crest cartilage of three patients and extracted the proteoglycan monomers from one of the samples. Sections of iliac-crest cartilage and proximal fibular growth plates were examined by electron microscopy and also stained with hematoxylin and eosin, safranin O-fast green, and alcian blue in the presence of increasing concentrations of magnesium chloride (zero to one molar). The chondrocytes of the iliac crest and fibular physes were arranged in clusters more than in columns and contained characteristic endoplasmic reticulum inclusions, which were particularly large in the hypertrophic cells. The cartilage stained very poorly with hematoxylin and eosin and with safranin O-fast green. The alcian-blue stain was abolished from perilacunar areas and from longitudinal septa by magnesium chloride concentrations that were lower than those required by normal tissue. The proteoglycans of iliac-crest cartilage were found to be significantly enriched in keratan sulphate and had a below-normal ratio of chondroitin-4-sulphate to chondroitin-6-sulphate, although the amount of the two isomeric chondroitin sulphates combined was within normal limits. The urinary excretion of glycosaminoglycan by the three patients was normal. Pseudoachondroplasia appears to be a generalized cartilage disorder involving abnormalities of proteoglycans, probably related to the core protein or to enzymes that are responsible for the formation of the glycosaminoglycan chains.(ABSTRACT TRUNCATED AT 250 WORDS)