Mucopolysaccharidoses

MUCOPOLYSACCHARIDOSES

Harish S. Hosalkar MD, MBMS (Orth), FCPS (Orth), DNB (Orth)    

IntroductionMucopolysaccharidoses (MPS) are a group of inherited metabolic disorders caused by deficiency of specific lysosomal enzymes, which results in intracellular accumulation of partially degraded glycoaminoglycans. Overall incidence of the MPS is one in 25,000 live births. 
The MPS are subdivided based on their enzyme deficiency and the type of substance that accumulates (Table 1).
 
TABLE 1.     Mucopolysaccharidoses and specific enzyme deficiencies
 Mucopolysaccharidoses (MPS)         Enzyme deficiency                             Gene locus
MPS I (Hurler syndrome)                 Alpha-L-iduronidase                           chromosome 4
MPS II (Hunter's disease)                 Iduronate-2-sulfatase                          X chromosome               
MPS III (Sanfilippo syndrome)           
      type A                                           Heparan sulphate sulphatase
      type B                                           Alpha-N-acetylglucosaminidase
      type C                                           Acetyl CoA: alpha-glucosaminide-                       
                                                            N-acetyltransferase 
      type D                                           N-acetyl-glucosaminide-6-               chromosome 12
                                                            sulphatase
MPS IV (Morquio syndrome)
      type A                                          Galactosamine-6-sulphate-
                                                           sulphatase
     type B                                           Beta-galactosidase
MPS VI (Polydystrophic                  Arylsulphatase B                                chromosome 5
 dysplasia)   

Although there is phenotypic variability, these disorders share some common clinical features, such as facial dysmorphism, short stature, organomegaly, cardiac problems, and joint contractures.  Mental retardation may be associated with some types. Most of the MPS show similar changes in the cartilage; resting cartilage consists of uniformly stained matrix, with chondrocytes that are larger than normal and stain positively for glycosaminoglycans. The most common of the MPS are Morquio and Hurler syndrome. The MPS can be diagnosed by some laboratory studies after birth.
 
The mucopolysaccharides, including heparan sulfate, dermatan sulfate, and keratin sulfate, are accumulated and excreted by the urine. Biochemical analysis of the urine can lead to the diagnosis of the specific MPS. Identification of the MPS is also possible through skin fibroblast culture. The fibroblasts are assayed for specific enzyme activity known to be abnormal in the different MPS.
Molecular genetic research determines the specific mutations that result in MPS. Specific mutations are described individually for each type of MPS (Table 1).
 

 Clinical Features

-          The clinical diagnosis of MPS is usually made between 6 months to 6-10 years of age, depending on the type.
-          A flat nasal bridge, hypertelorism, and corneal clouding are typical facial features seen in children with MPS.
-          Short stature, short neck, and joint contractures occur almost in all types.
-          Cervical instability and thoracolumbar kyphoscoliosis are common spinal problems.
-          Dysplasia of the pelvis, and broadening and shortening of the long bones may be seen.
-          Generalized joint laxity is a feature of Morquio syndrome, making it distinctly different from the other mucopolysaccharidoses, in which joint stiffness is the rule.
-          The patients with MPS I (Hurler syndrome) and MPS IV (Morquio syndrome) are usually more severely affected than the other types.
 

Radiographic Findings
 
The MPS may share some common radiographic findings.
-          Radiographic changes are commonly seen in the skull; the skull is enlarged, with a thick calvarium.
-          The clavicles are broad, especially medially. The ribs are oar-shaped and broader anteriorly than posteriorly.
-          The vertebral bodies are ovoid when immature. Scoliosis and kyphosis are frequently present.
-          The iliac wings are flared and the acetabulae are dysplastic. Coxa valga is common, and the long bones often have thickened cortices.
-          There is delay in ossification of the carpal bones.
It is difficult to differentiate the various types of MPS on the basis radiographic findings alone.
 

Orthopaedic Considerations
 
Genetic counseling is essential for all children diagnosed as MPS. Medical problems require appropriate treatment. Orthopaedic treatment usually consists of symptomatic corrective measures; fusion of cervical spine instability and conservative or surgical treatment of spinal curvatures and joint contractures.