Mucopolysaccharidoses and Orthopedic Management (Focused also on Craniocervical Junction)

Abstract

Mucopolysaccharidoses (MPSs) are multisystemic, chronic progressive, heterogeneous, and life-threatening diseases, involving severely the musculoskeletal system, in particular in MPS I, II, IV, VI, VII, and less prevalent in MPS III. Accumulation of glycosaminoglycans (GAGs) in soft tissues, such as ligaments, tendons, and joint capsules, as well as in cartilage, and bone lead to orthopedic complications: joint stiffness, contractures, and skeletal deformities, resulting in hip dysplasia, genua valga, feet deformities, kyphoscoliosis, narrowing of the spinal canal, atlantoaxial instability, carpal tunnel syndrome, trigger finger, and growth retardation. These complications significantly reduce the quality of life due to impaired mobility, loss of independency, and pain. Compression of the cervical spinal cord is also life threatening. According to the progressive nature of MPSs, musculoskeletal symptoms worsen over time and surgical intervention may be inevitable. However, due to the increased anesthesia risk of MPSs, surgical intervention has to be evaluated carefully by a multidisciplinary team. Additionally, due to the rarity of the diseases, not many standards or recommendations are available to determine the indication of a surgical intervention, so each intervention must be decided individually, based on the few data available. In addition, conservative treatment should be taken into consideration. Physiotherapy, pain medication, insoles, orthosis, braces, corsets, and special footwear play a pivotal role. Unfortunately, the skeletal tissues are poorly vascularized and enzyme replacement therapy does not have much effect on them. It is important to detect and observe musculoskeletal complications in the regular follow-up visits, in particular the life-threatening compression of the cervical spinal cord.

The surgical management of spinal disorders in lysosomal storage diseases: a systematic review

“…Sixteen articles discussed the surgical management of the various mucopolysaccharidoses as a group 8,9,19,24–26,29–38 . Four specifically discussed MPS‐I, 11,12,28,39 eight MPS‐IV, 40–47 and five MPS‐VI 18,48–51 .…”

“…Surprisingly, the presence of myelopathy or neurological deterioration was only considered an indication for surgery in twelve studies. 8,12,19,25,28,29,[34][35][36][37][38][39] More commonly, fourteen studies stated that the severity of the deformity determines the need for surgery, however there was considerable heterogeneity as to the degree of deformity that constitutes a surgical indication. 8,12,19,[24][25][26]28,30,[35][36][37][38][39]52 Roberts et al 35 patients with 38 of kyphosis or more should be considered for surgery.…”

“…8,12,19,25,28,29,[34][35][36][37][38][39] More commonly, fourteen studies stated that the severity of the deformity determines the need for surgery, however there was considerable heterogeneity as to the degree of deformity that constitutes a surgical indication. 8,12,19,[24][25][26]28,30,[35][36][37][38][39]52 Roberts et al 35 patients with 38 of kyphosis or more should be considered for surgery. Five articles stated that 40 warrants surgical intervention, 8,19,25,26,38 two studies said 45 , 24,37 one study stated 60 , 30 and one study recommended surgery for kyphotic angles of 70 or more.…”

“…Sixteen articles discussed the indications for cranio‐cervical surgery in MPS. Evidence of cervical myelopathy or progressive neurological compromise was unanimously accepted as a surgical indication 8,18,25,31,34,36,37,41–44,46–49,51 . Cervical spinal cord signal change on MRI was considered an indication for surgery in six studies, 31,36,41,42,44,47 while pathological reflexes on neurological examination were reported as an indication in two studies 41,44 .…”

Disruption of morphogenic and growth pathways in lysosomal storage diseases

“…the forebrain, in axon guidance errors, and in abnormalities of bone development (Bandari et al, 2015;De Pasquale & Pavone, 2019). MPS patients exhibit severe spine deformities, including progressive kyphoscoliosis and spinal cord compression (Lampe & Lampe, 2018;Muenzer et al, 2009). An imbalance of chondrocyte hypertrophic differentiation rate during the process of cartilage to bone transition was shown in MPS VII dogs, leading to a delay in the endochondral bone formation (Smith et al, 2012).…”