FELINE MUCOPOLYSACCHARIDO

SIS Christina Copple, DVM

Radiology ResidentNCSU CVM-VTHApril 13, 2009

Accession #57629

Feline Mucopolysaccharidosis (MPS)

►Uncommon, autosomal recessive inherited disorder = reduction or absence of glycosaminoglycan (GAG) dermatan sulfate catabolism

►> 10 forms are recognized in humans due to various enzyme defects Many of the same forms have been

recognized in both canines and felines

Feline Mucopolysaccharidosis (MPS)

► Lysosomal degradation of mucopolysaccharides is necessary for normal growth

►Undegraded product is stored in tissues and excreted in the urine

►Abnormal catabolism → chronic, progressive, and multisystemic disease Stimulation of inflammation and apoptosis in cartilage and

synovial cells► Two subclasses have been identified in cats (esp. those

of Siamese ancestry) MPS I MPS VI

Feline Mucopolysaccharidosis (MPS)MPS I

►Deficiency of alpha1-iduronidase►DSH cat►Similar clinical features as MPS VI

Lacks bony proliferative changes, spinal cord compression and neurologic deficits

MPS VI►Deficiency of lysosomal enzyme:

arylsulfatase B►Siamese cats

http://www.dkimages.com/discover/previews/928/60025166.JPG

Clinical Features of MPS VI► Physical deformities noticeable by 8 weeks of age

(facial dysmorphia & disproportionate dwarfism): Small head Flat and broad face Wide spaced eyes Depressed bridge of nose Small ears Large forepaws Pectus excavatum Generally smaller than littermates

► Corneal opacification► Cardiac valvular thickening► Skeletal changes:

Fusion of cervical vertebrae Variable fusion of thoracic and lumbar vertebrae Hyperextension of distal extremity joints due to laxity

► Bony proliferation: In the intervertebral foramina causes nerve root

compression Into the vertebral canal causes compression of the

spinal cord

MPS VI►Bony proliferative changes and associated

spinal cord compression occur prior to or at the time of epiphyseal closure (~ 9 mths). These changes are probably nonprogressive after this point.

►Neurologic deficits (indicative of a transverse T3-L3 myelopathy) are seen between 4 -7 mths of age with progression over the next 2 -4 weeks. Loss of conscious proprioception in the pelvic

limbs Normal to increased pelvic limb reflexes Decreased pain perception in the pelvic limbs

Accession #57629

Radiographic changes of both the axial and appendicular skeleton:

• generalized epiphyseal dysplasia of long bones and vertebral endplates

• delayed and incomplete mineralization of the epiphyseal cartilage model

• ossified regions of the epiphyses are smaller than normal & have a nonuniform opacity with a granular appearance

• vertebral bodies are shorter than normal and cuboid in shape

• maxilla is short and flat• frontal sinuses are small or absent• hip subluxation or luxation may result from

femoral head epiphysis remodeling

Diagnosis and Treatment of MPS VI

►Signalment, clinical signs and radiographic abnormalities of the spine

►Measure arylsulfatase B activity in leukocytes

►Potential for decompressive surgery of the spine after 9 mths of age since disease is nonprogressive Possible to have multiple sites of compression

►No treatment for the lysosomal enzyme deficit Bone marrow transplantation?? Enzyme replacement therapy??

Radiographically Visualized Skeletal Changes Associated With Mucopolysaccharidosis VI In

CatsKonde, Thrall, Gasper, Dial, McBiles, Colgan, and

HaskinsVetRad, 28:6, 1987. pp223-228► Characterized radiographic abnormalities of 11 cats

of Siamese ancestry with MPS VI► Definitive diagnosis via:

Measurement of increased urinary GAG excretion Presence of typical Alder-Reilly bodies in neutrophils Absence of measurable leukocyte arylsulfatase-B activity

► Most severe changes centered in areas of enchondral ossification: accumulation of GAG inhibits normal transition from cartilage to bone in the physis and on bone formation in epiphyseal ossification centers

► Diseases with similar radiographic appearance: congenital hypothyroidism, epiphyseal dysplasia, hypervitaminosis A, and hyperparathyroidism

Radiographically Visualized Skeletal Changes Associated With Mucopolysaccharidosis VI In

CatsKonde, Thrall, Gasper, Dial, McBiles, Colgan, and

HaskinsVetRad, 28:6, 1987. pp223-228► All affected cats had severe decreased bone opacity

with thin cortices and a coarse trabecular pattern► Epiphyseal dysplasia► Abnormal nasal turbinate development► Coxofemoral subluxation► Impaired development of skeletal growth► Pectus excavatum► Hyoid hypoplasia► Aplasia, hypoplasia, and fragmentation or abnormal

ossification of the dens► Aplasia or hypoplasia of frontal and sphenoid

sinuses

VetRadUS, 28:6, 1987. pp223-228

VetRadUS, 28:6, 1987. pp223-228

Normal

MPS VI

References► Ettinger, Stephen J., DVM and Edward C. Feldman, DVM. Textbook of

Veterinary Internal Medicine Diseases of the Dog and Cat. 6th ed. Volume I. Elsevier, St. Louis, MO. 2005. 872-873.

► Thrall, Donald E., DVM, PhD. Textbook of Veterinary Diagnostic Radiology. 5th ed. Saunders, St. Louis, MO. 2007. 276-277.

► Konde, Linda J., DVM, Mary Anna Thrall, DVM, MS, Peter Gasper, DVM, PhD, Sharon M. Dial, DVM, Kit McBiles, Sean Colgan, Mark Haskins, VMD, PhD. Radiographically Visualized Skeletal Changes Associated With Mucopolysaccharidosis VI In Cats. Veterinary Radiology, 28:6, 1987. 223-228.

► Yogalingam, Gouri, Tom Litjens, Julie Bielicki, Allison C. Crawley, Vivienne Muller, Donald S. Anson, and John J. Hopwood. Feline Mucuopolysaccharidosis Type VI: Characterization of Recombinant N-Acetylgalactosamine 4-Sulfatase and Identification of a Mutation Causing The Disease. The Journal Of Biological Chemistry. 271:44, November 1996. 27259-27265.

► Simonaro, Calogera M., Marina D’Angelo, Xingxuan He, Efrat Eliyahu, Nataly Shtraizent, Mark E. Haskins, and Edward H. Schuchman. Mechanism of Glycosaminoglycan-Mediated Bone and Joint Disease: Implications for the Mucopolysaccharidoses and Other Connective Tissue Diseases. The American Journal of Pathology. 172:1, January 2008. 112-122.