What are the musculoskeletal manifestations of MPS?
MPS are a group of metabolic disorders affecting 1 in 25,000 births that are caused by the absence or malfunctioning of one of the 11 lysosomal enzymes needed to break down glycosaminoglycans (formerly called mucopolysaccharides). Seven distinct MPS types have been identified. All are autosomal recessive except for MPS II (Hunter), which is X-linked recessive. Catabolites of glycosaminoglycans are progressively deposited in various tissues. This deposition leads to skeletal dysplasia, which characteristically causes short stature, joint contracture, stiff joints, carpal tunnel syndrome, and claw-hand deformity. Thick calvaria, an enlarged J-shaped sella turcica, a short and wide mandible, biconvex vertebral bodies, odontoid hypoplasia with atlantoaxial instability, short thick clavicles, coxa valga, V-shaped deformities of the distal ulna and radius, and short fingers with wide metacarpals with pointed proximal ends all occur. Many individuals affected by MPS have mental retardation, thick skin, corneal clouding, heart murmurs, and organomegaly. The Hurler, Hunter, Morquio, and Maroteaux–Lamy syndromes (types I-H, II, IV, and VI) have short-trunk dwarfism, but attenuated forms (types I-HS, I-S, II, IVB, and VI) caused by various genetic mutations can have relatively normal stature. A diagnosis of MPS is made by fractionation of urinary glycosaminoglycans, enzyme assays, and/or molecular genetics. Treatment is palliative and consists mainly of joint replacement and surgical stabilization of cervical instability. Bone marrow transplants have been successful in some forms of MPS (type I). Enzyme replacement therapy has been beneficial for MPS I treated with α-L-iduronidase (laronidase, Aldurazyme), MPS II with iduronidase sulfatase (idursulfase, Elaprase), MPS IVA with N-acetylgalactosamine-6-sulfatase (elosulfase alfa, Vimizim), and MPS VI with arylsulfatase B (galsulfase, Naglazyme).
