Caprine beta-mannosidosis. Abnormal thyroid structure and function in a lysosomal storage disease.

Deficient activity of the lysosomal enzyme beta-mannosidase leads to widespread tissue accumulation of oligosaccharides in caprine beta-mannosidosis, an autosomal recessive neurovisceral storage disease. Severe thyroid morphologic abnormalities found in a previous light microscopic survey of tissues from neonatal affected goats suggested the possibility of impairment of function. Since considerable evidence indicates that thyroid hormone plays an important role in regulation of myelination, thyroid hormone deficiency, if present during central nervous system development, could be a factor in the hypomyelination seen in affected animals. Thus, this study was designed to characterize thyroid structure and function in beta-mannosidosis. To investigate developmental aspects of structural abnormalities, thyroids from six pairs of affected and control animals ranging in age from 96/150 days gestation to 3 days postnatal were analyzed by light and electron microscopy. Major findings in thyroids from affected animals, as early as 96/150 days gestation, included follicle irregularities and pronounced presence of lysosomal storage vacuoles in all cell types, particularly in follicular cells. The degree of cytoplasmic vacuolation increased with advancing age. To assess thyroid function, thyroid hormone concentrations were determined in six age-matched, neonatal pairs of affected and control goats. Significantly decreased thyroid hormone concentrations were present in affected animals. It is hypothesized that thyroid hormone deficiency plays a role in the pathogenesis of hypomyelination in affected animals. This study comprises, to our knowledge, both the most complete description of developmental abnormalities and the first report of abnormal function in an endocrine organ in a lysosomal storage disease. Further, this report suggests that systemic perturbations induced by a genetically determined deficiency of a lysosomal hydrolase could be a factor in the pathogenesis of central nervous system lesions.