Mucopolysaccharidosis Type I (MPS 1) Orthopedic Manifestations & Treatments

Orthopedic manifestations cause significant morbidity and discomfort to individuals with mucopolysaccharidosis type I (MPS I). Orthopedic concerns include:

• Progressive arthropathy leading to severe joint deformity (occurs in all patients)
• Early bone involvement, with diminution of linear growth by age 3 in children with severe MPS I
• Carpal tunnel syndrome is common, but early symptoms (pain, tingling, and numbness) often go unreported. More commonly, parents notice increased difficulty with fine motor skills (a late symptom) or gnawing on fingertips.

Individuals with attenuated MPS I may have severe progressive bone involvement despite absence of cognitive impairment. Joint stiffness and contractures may present initially in the fingers resulting in the characteristic "claw hand." Progressive skeletal dysplasia, or dysostosis multiplex, is seen in all individuals with severe MPS I. Dysostosis multiplex congenita is a radiologic finding with a number of related features, including:

• Dolichocephaly
• Spatulate ribs (oar-like)
• Wide diaphyses and narrow epiphyses
• Wide metacarpals, phalanges, metatarsals (bullet-like)
• Hypoplastic acetabulae
• Kyphoscoliosis (gibbus deformity)
• Anterior beaking of vertebrae
• Platyspondyly
• Ossification defects of the lower vertebral bodies

Complications may include:

• Spinal nerve entrapment, including sciatica
• Acute spinal injury
• Atlanto-occipital instability
• Knees that are prone to valgus and varus deformities
• Pelvic abnormalities
• Carpal tunnel syndrome
• Progressive and debilitating hip deformity leading to early hip replacement
• Resultant joint pain

While orthopedic surgery may greatly enhance the quality of life, there are significant risks for MPS I patients who undergo general anesthesia. Procedures that require general anesthesia should be conducted in an experienced center that is aware of the risks in this population:

• Dysostosis multiplex can lead to instability of the spine, including the atlantoaxial joint. Careful positioning and avoidance of hyperextension of the neck are necessary.
• Maintaining an adequate airway for induction of anesthesia can be difficult.
• Smaller than anticipated endotracheal tubes are often required because the trachea may be narrowed and the vocal cords thickened.

Spinal cord compression or instability of the neck may result in myelopathy (and rarely quadriparesis). Patients should be instructed to avoid "high-risk" activities, such as contact sports, and parents should be cautioned about manipulation of the cervical spine. Neurosurgical stabilization of the spine may be indicated for those with signs of cord compression.

Thoracolumbar kyphosis (gibbus deformity), due to poor bone growth in the anterior vertebrae, occurs in about 90% of patients with severe MPS I and is the most common orthopedic abnormality. Prior to hematopoietic stem cell transplant, surgery for gibbus deformities was not performed on patients with MPS I due to their limited life expectancy. Following hematopoietic stem cell transplant, kyphosis will progress in about a third of patients and surgery will be required before age 9; in another third, it will not progress and surgery may be required later; kyphosis will improve in the remaining patients.

Myelopathy and respiratory problems can occur later in life if kyphosis is left untreated. Bracing may slow the progression of kyphosis and scoliosis, delaying but not preventing surgery. However, bracing is often not tolerated by young children and generally not recommended.

The presence of myelopathy is also an indication for surgery.

• Surgery for kyphosis almost always requires incisions from the front and the back.
• Metal hardware is typically stainless steel or titanium and is generally not removed unless there are complications.
• Most children will require some combination of a cast or brace for between 3 months and a year.
• An unsuccessful fusion can be painful and require repeat surgery.

Scoliosis may accompany kyphosis. When left untreated, scoliosis can lead to difficulty expanding the chest wall. Delaying spinal surgery may allow for maximal growth of the spine and further development of already dysplastic bone.

Hip dysplasia, to some degree, is found in nearly all children with severe MPS I. It is not responsive to hematopoietic stem cell transplant or enzyme replacement therapy; the majority of children eventually require corrective surgery. Without hip surgery, there is progressive pain and stiffness and eventually frank dislocation of the hips with a dramatic reduction in walking ability. Surgery involves repositioning the bones and tightening the soft tissues around the hip.

Genu valgum (knock-knees) severe enough to require surgery occurs in about 50% of children with severe MPS I post-transplant. The indication for surgery is a knee deformity greater than 15 degrees. Children with MPS I also suffer from stiff knees, which prevent full extension and result in a crouched gait. Physical therapy can optimize knee motion and enhance walking. Knee staples are placed in the bone on the inner side of the knee to prevent bone growth on the inner side to allow the outer side to catch up. Occasionally, the staples dislodge and may need to be removed and replaced. In small children, staples will not work and osteotomies in large bones around the knees may be required.

Carpal tunnel syndrome, trigger digits, and contractures of the fingers are common. Since there is a high incidence of undetected carpal tunnel syndrome, close monitoring is recommended, including regular evaluation by an occupational therapist preferably specialized in hands. Surgery consists of releasing the constricting tissue over the median nerve and removing the deposits on the surrounding tendons. Trigger digits are treated by opening 1 or 2 of the many pulleys in each finger and cleaning the tendons of GAG material. These surgeries are relatively minor but may be beneficial.