Retarded bone formation in GM1-gangliosidosis: a study of the infantile form and comparison with two canine models

Abstract

The development of skeletal lesions in two canine models of GM1-gangliosidosis, English springer spaniels and Portuguese water dogs, has been studied and compared to osseous abnormalities in a child with the infantile form of the disease. In the canine models, skeletal dysplasia was progressive. Lesions were noted at 2 months of age and characterized by retarded endochondral ossification and osteoporosis. Older puppies had focal cartilage necrosis within lumbar vertebral epiphyses. At the cellular level, lesions were characterized by chondrocytic hypertrohy and lysosomal accumulation of storage compounds. Our studies illustrate that the skeletal lesions in both canine models are similar to those in a child with GM1-gangliosidosis. Furthermore, we proposed that the abnormal storage of partially degraded compounds in affected chondrocytes might explain, at least in part, the retarded bone formation noted in patients with GM1-gangliosidosis.

GM1-gangliosidosis in Alaskan Huskies: Clinical and Pathologic Findings

“…The disease in Alaskan Huskies showed similarities to GM 1 -gangliosidosis in other dogs. The age of onset, neurologic signs, and rapid progression were similar to GM 1 -gangliosidosis of ESS, PWD, 2,3,33,35,36 and mixed-breed Beagles. 34 Proportional dwarfism has only been reported in ESS 3 and Alaskan Huskies.…”

“…38 The disease has been described in a variety of species, including cats, cattle, sheep, mice, and humans. [1][2][3][4][5][6][7][8][9]12,14,16,17,[27][28][29]31,[33][34][35][36][37][38] Until now, the canine form has been found in English Springer Spaniels (ESS), 3,33 Portuguese Water Dogs (PWD), 3,35,36 mixed-breed Beagles, 34 and Alaskan Huskies. 28 In humans, the disorder is classified as infantile (type 1), juvenile (type 2), and adult (type 3) forms.…”

Secondary biochemical and morphological consequences in lysosomal storage diseases

“…Skeletal abnormali ties associated with storage of keratan sulfate are observed in MPS IVA and MPS IVB [125] as well in G M1 gangliosidosis [145]. Poorly developed primary spongio sis and metaphysical osteopetrosis were demonstrated in growth plates of vertebral epiphyses in 2 month old dogs, and focal epiphyseal cartilage necrosis was noted in 9 month old dogs with G M1 gangliosidosis [146]. Shortened bones were observed in the case of MPS VII related β glucuronidase deficiency resulting in accumu lation of chondroitin 4 sulfate at the growth plates with subsequent decrease in proliferation of chondrocytes in growth zones.…”

Case series of two siblings suffering from GM1 gangliosidosis resulting in early multiple joint arthroplasties

“…There have been reports of progressive skeletal dysplasia and skeletal lesions characterised by retarded endochondral ossification in vertebral epiphyses leading to premature avascular necrosis of joints [8][9][10]. Gaucher disease, the most common of the lysosomal storage diseases, has many hallmarks of chronic inflammation related to microvascular occlusion including avascular necrosis [6,7].…”

“…Animal studies and in vitro models have shown a correlation of skeletal abnormalities with gangliosidosis [9]. There have been reports of progressive skeletal dysplasia and skeletal lesions characterised by retarded endochondral ossification in vertebral epiphyses leading to premature avascular necrosis of joints [8][9][10].…”