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)