Hyaline cartilage changes in diastrophic dwarfism

Abstract

Hyaline cartilage of the talus of a diastrophic dwarf was studied by light and transmission electron microscopy before and after proteoglycan extraction or digestion, glycogen digestion, and enzyme marking. The nuclei of the chondrocytes were as a rule large and round and the cytoplasm contained large vacuoles. Best's carmine stained the cytoplasm of most cells red; after diastase digestion the cytoplasm remained unstained. This suggested that the cells contained glycogen. This observation was complimented by the ultrastructural demonstration of large amounts of glycogen. Cell scars were frequent. The shape and state of activity of the cells as well as the development of intracytoplasmic organelles showed great variability. The matrix showed many areas of degeneration and a general dearth of sulphated acid mucopolysaccharides. A lacey pattern of unmasked collagen fibers was frequently seen. Collagen fibers showed a great variability in diameter and often appeared frayed when examined by electron microscopy. These observations suggest an enzymatic deficiency in chondrocyte mucopolysaccharide and glucose metabolism. The techniques we used when added to biochemical studies should prove useful in the investigation of human dwarfism.

Atelosteogenesis type II: Sonographic and radiological correlation

“…In A 0 type 11, the second and/or third metacarpals and metatarsals are much larger than the rest of the bones in the hands or feet; the ribs are slightly shortened with cupped ends; there is lumbosacral hyperlordosis with a horizontal sacrum; and the acetabulum is flat, hypoplastic, and horizontal. Histopathological changes in diastrophic dysplasia include enlarged and ovoid reserve zone chondrocytes with large cytoplasmatic vacuoles irregularly distributed throughout the matrix, degenerating cells surrounded by a rim of fibrousappearing debris, and thick collagen fibres with abnormal periodicity (Scheck et al, 1978;Sillence e f al., 1979).…”

Diastrophic dysplasia gene maps to the distal long arm of chromosome 5.

“…In recessive disorders like DD, abnormalities in genes coding for structural proteins may be less likely than mutations in genes encoding proteins affecting connectivetissue metabolism. For instance, it has been suggested that an enzymatic deficiency in chondrocyte mucopolysaccharide and glucose metabolism might cause the disease (27). However, confirmative evidence has not been reported.…”

Abnormality of type IX collagen in a patient with diastrophic dysplasia

“…The clinical presentation includes short stature, micromelia, cleft palate, cauliflower ears, clubfoot (which may be uni-or bi-lateral and which is often resistant to surgical correction), multiple major joint contractures, subluxations and dislocations, and possible neurological sequelae with spinal cord compression due to vertebral deformity [Bethem et al, 1980;Hollister and Lachman, 1979;Kite, 1964;Taber et al, 1973;Walker et al, 19721. Inheritance is autosomal recessive [McKusick and Milch, 19721, and the clinical course shows considerable variability, with both a rare lethal and a much more common non-lethal form of the disease distinguished [Gustavson et al, 19851. Even milder diastrophic variants have also been described LRimoin and Lachman, 19931. Morphological changes in diastrophic dysplasia cartilage observed on light microscopy include cytoplasmic accumulation of glycogen and fatty deposits in chondrocytes; variability of chondrocyte size, shape, and viability; non-uniformity of the matrix with fibrovascular ingrowth giving fibrotic foci; and areas of intracartilaginous calcification [Horton et al, 1979;Scheck et al, 1978;Shapiro, 19921. On transmission electron microscopy, collagen fibrils in the fibrous foci of the cartilage matrix have been shown to be abnormally thickened, clearly cross-banded, irregularly aggregated, and frayed [Horton et al, 1979;Scheck et al, 1978;Shapiro, 19921.…”

“…Even milder diastrophic variants have also been described LRimoin and Lachman, 19931. Morphological changes in diastrophic dysplasia cartilage observed on light microscopy include cytoplasmic accumulation of glycogen and fatty deposits in chondrocytes; variability of chondrocyte size, shape, and viability; non-uniformity of the matrix with fibrovascular ingrowth giving fibrotic foci; and areas of intracartilaginous calcification [Horton et al, 1979;Scheck et al, 1978;Shapiro, 19921. On transmission electron microscopy, collagen fibrils in the fibrous foci of the cartilage matrix have been shown to be abnormally thickened, clearly cross-banded, irregularly aggregated, and frayed [Horton et al, 1979;Scheck et al, 1978;Shapiro, 19921.…”