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Craniofacial abnormalities in animal models of mucopolysaccharidoses I, VI, and VII
O Sheridan1, J Wortman, C Harvey
1School of Dental Medicine, University of Pennsylvania, Philadelphia 19104-6051.
Abstract:
The genetic mucopolysaccharidoses (MPS) are a family of lysosomal storage diseases resulting from the partial catabolism of several glycosaminoglycans (GAGs). Depending on the particular enzyme deficient in activity, the MPS syndromes are defined into groups MPS I through VII, with several subgroups for a total of 10 disorders. In humans, clinical features include dysostosis multiplex, hepatosplenomegaly, hypertelorism, macroglossia, hypoplastic and irregularly shaped teeth, hyperplastic lips and gingiva, facial dysmorphia, corneal clouding, and mental retardation. MPS I (alpha-L-iduronidase deficiency) and VI (arylsulfatase B deficiency) have been described in cats, MPS VII (beta-glucuronidase deficiency) in dogs. Biochemically, these syndromes appear the same as their human counterparts and have similar clinical characteristics. All are inherited as autosomal recessive traits. The purpose of this study was to analyze the craniofacial aspects of these diseases in the animal models and compare these data with descriptions of the human syndromes. A total of 28 live animals were examined. Thirty-one skulls prepared from postmortem specimens were measured directly and radiographed. Controls were closely related family members of the same sex and similar age without the disease, clinically or biochemically. The data indicated that, as in the human syndromes, each is distinct, and the skull bones most severely affected are those of endochondral origin.
Insights
Mucopolysaccharidoses (MPS) are genetic lysosomal storage diseases affecting bone development. This study analyzed craniofacial aspects in animal models, finding distinct patterns similar to human MPS syndromes, with endochondral bones most impacted.
Area of Science:
- Genetics
- Biochemistry
- Veterinary Medicine
Background:
- Mucopolysaccharidoses (MPS) are genetic lysosomal storage diseases caused by impaired glycosaminoglycan (GAG) catabolism.
- These disorders manifest with diverse clinical features, including skeletal abnormalities, organomegaly, and cognitive impairment.
- MPS I, VI, and VII have been identified in cats and dogs, exhibiting biochemical and clinical similarities to human counterparts.
Purpose of the Study:
- To investigate and compare the craniofacial characteristics of MPS in animal models (cats and dogs) with human MPS syndromes.
- To analyze the specific skeletal regions affected by MPS in these animal models.
Main Methods:
- Examination of 28 live animals and radiographic analysis of 31 postmortem skulls.
- Direct measurements and radiographic imaging were performed on affected animals and age/sex-matched controls.
- Clinical and biochemical assessments were used to confirm disease status in controls.
Main Results:
- Each MPS type in animal models presented distinct craniofacial features, mirroring human presentations.
- The most significantly affected bones were those of endochondral origin.
- The study confirmed the autosomal recessive inheritance pattern for these conditions.
Conclusions:
- Animal models of MPS exhibit distinct and comparable craniofacial phenotypes to human syndromes.
- Endochondral ossification sites are particularly vulnerable to the effects of MPS.
- These findings support the use of animal models for studying MPS pathogenesis and potential therapies.