Skeletal involvement in severe MPS I patients can be detected in the first year of life by radiological methods., At that time, it is common to observe mild bone abnormalities, particularly within the hip, ovoid vertebrae, as well as widening of the ribs. Clinically, skeletal involvement does not become obvious until the age of 6-14 months when a gibbus deformity of the back or dorsolumbar kyphosis is observed (Image 1).
Image 1 - Gibbus deformity
Courtesy of E. Kakkis, MD
Eventually, progressive skeletal dysplasia involving all bones is seen in all types of MPS I. The constellation of skeletal abnormalities is known as dysostosis multiplex.
The most notable features are defective centers of ossification of the vertebral bodies leading to ovoid vertebrae. The vertebrae become progressively flattened and beaked, often leading to spinal deformity. Complications may include spinal nerve entrapment, acute spinal injury, and atlanto-occipital instability. Long bones do not properly remodel and become short with irregular wide shafts and tilting of the epiphyses, leading to valgus and varus deformities. Typically the pelvis is poorly formed, with small femoral heads and coxa valga. Involvement of the femoral head leads to progressive and debilitating hip deformity. Clavicles are short, thickened and irregular. By three years of age there is little progression of physical (linear) growth. The joints often become stiffened by the age of two years and progressive arthropathy may affect joints. The hands may also take on a characteristic joint contracture deformity resulting from both phalangeal dysostosis and synovial thickening (Image 2).
Image 2 - Joint Contractures
Courtesy of the National MPS Society
Carpal tunnel syndrome and interphalangeal joint involvement commonly lead to poor hand function in all forms of MPS I., Carpal tunnel syndrome is often missed because its onset is insidious and often present with few or no symptoms except thenar atrophy.
Joint replacement and specific neurosurgical approaches may be required to address spinal involvement, including atlanto-occipital stabilization. Physical therapy can also play a role, and its benefits in MPS I patients deserve further research. Range of motion exercises appear to offer some benefits in preserving joint function. Once significant limitation has occurred, increased range of motion may not be achieved in the patient, but exercises may serve to minimize further limitation.
In MPS I, glycosaminoglycan (GAG)-engorged cells accumulate and displace healthy normal cells in tissue and organs such as the liver and spleen, causing a host of signs, including skeletal deformities, coarse facial features, and an enlarged liver and spleen.