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Patients with mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) have accumulation of the glycosaminoglycans, keratan sulfate, and chondroitin-6-sulfate, in bone and cartilage, causing systemic spondyloepiphyseal dysplasia. Features include lumbar gibbus, pectus carinatum, faring of the rib cage, marked short stature, cervical instability and stenosis, kyphoscoliosis, genu valgum, and laxity of joints. Generally, MPS IVA patients are wheelchair-bound as teenagers and do not survive beyond the second or third decade of life as a result of severe bone dysplasia, causing restrictive lung disease and airway narrowing, increasing potential for pneumonia and apnea; stenosis and instability of the upper cervical region; high risk during anesthesia administration due to narrowed airway as well as thoracoabdominal dysfunction; and surgical complications. Patients often need multiple surgical procedures, including cervical decompression and fusion, hip reconstruction and replacement, and femoral or tibial osteotomy, throughout their lifetime. Current measures to intervene in disease progression are largely palliative, and improved therapies are urgently needed. A clinical trial for enzyme replacement therapy (ERT) and an investigational trial for hematopoietic stem cell transplantation (HSCT) are underway. Whether sufficient enzyme will be delivered effectively to bone, especially cartilage (avascular region) to prevent the devastating skeletal dysplasias remains unclear. This review provides an overview of historical aspects of studies on MPS IVA, including clinical manifestations and pathogenesis of MPS IVA, orthopedic surgical interventions, and anesthetic care. It also describes perspectives on potential ERT, HSCT, and gene therapy.

Mucopolysaccharidosis type I (MPS I; Hurler Syndrome) is a lysosomal storage disease caused by a deficiency of the enzyme α-L-iduronidase which affects multiple organs such as central nervous system (CNS), skeletal system, and physical appearance. Hematopoietic stem cell transplantation (HSCT) is recommended as a primary therapeutic option at an early stage of MPS I with a severe form to ameliorate CNS involvement; however, no description of pathological improvement in skeletal dysplasia has been investigated to date. We here report a 15-year-old male case with MPS I post-HSCT. This patient received successful HSCT at the age of 2 years and 1 month, followed for over 10 years. His activity of daily living including cognitive performance has been kept normal and the present height and weight are 162 cm and 55 kg. Bone deformity has been still developed, resulting in hemiepiphysiodesis of bilateral medial proximal tibia at 12 years of age and successive arthrodesis of thoraco-lumbar spine at 13 years of age; however, skeletal histopathology from surgical remnants showed substantial improvement in bone lesion with markedly reduced occurrence and cell size of vacuolated cells. After a series of surgical procedures, he became ambulant and independent in daily activity. The levels of GAGs in blood were substantially reduced. In conclusion, this long-term post-HSCT observation should shed light on a new aspect of therapeutic effect associated with skeletal pathology and GAG levels as a biomarker, indicating that HSCT is a primary choice at an early stage for not only CNS but skeletal system in combination of appropriate surgical procedures.

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a b s t r a c t a r t i c l e i n f oMucopolysaccharidosis type I (MPS I; Hurler syndrome) is a lysosomal storage disease caused by a deficiency of the enzyme α-L-iduronidase which affects multiple organs such as central nervous system (CNS), skeletal system, and physical appearance. Hematopoietic stem cell transplantation (HSCT) is recommended as a primary therapeutic option at an early stage of MPS I with a severe form to ameliorate CNS involvement; however, no description of pathological improvement in skeletal dysplasia has been investigated to date. We here report a 15-year-old male case with MPS I post-HSCT. This patient received successful HSCT at the age of 2 years and 1 month, followed for over 10 years. His activity of daily living including cognitive performance has been kept normal and the present height and weight are 162 cm and 55 kg. Bone deformity has been still developed, resulting in hemiepiphysiodesis of bilateral medial proximal tibia at 12 years of age and successive arthrodesis of thoraco-lumbar spine at 13 years of age; however, skeletal histopathology from surgical remnants showed substantial improvement in bone lesion with markedly reduced occurrence and cell size of vacuolated cells. After a series of surgical procedures, he became ambulant and independent in daily activity. The levels of GAGs in blood were substantially reduced. In conclusion, this long-term post-HSCT observation should shed light on a new aspect of therapeutic effect associated with skeletal pathology and GAG levels as a biomarker, indicating that HSCT is a primary choice at an early stage for not only CNS but also skeletal system in combination of appropriate surgical procedures.

No abstract