Mucopolysaccharidosis type 4

Mucopolysaccharidosis type 4 (MPS IV), also known as Morquio syndrome, is a rare inherited lysosomal storage disorder caused by deficient breakdown of the glycosaminoglycans (GAGs) keratan sulfate and chondroitin-6-sulfate. There are two subtypes: MPS IVA (Morquio A syndrome), caused by deficiency of the enzyme N-acetylgalactosamine-6-sulfatase (GALNS gene), and MPS IVB (Morquio B syndrome), caused by deficiency of beta-galactosidase (GLB1 gene). Both subtypes lead to progressive accumulation of GAGs in tissues, predominantly affecting the skeletal system. The hallmark features of MPS IV include severe skeletal dysplasia with short trunk dwarfism, odontoid hypoplasia leading to atlantoaxial instability, kyphoscoliosis, pectus carinatum, genu valgum (knock knees), joint hypermobility, and waddling gait. Patients typically appear normal at birth, with symptoms becoming apparent in early childhood, usually between ages 1 and 3 years. Unlike some other MPS types, intelligence is generally preserved. Extraskeletal manifestations can include corneal clouding, hearing loss, dental enamel abnormalities, hepatomegaly, and cardiac valve disease. Cervical spinal cord compression due to odontoid hypoplasia is a serious and potentially life-threatening complication. Respiratory compromise from thoracic deformity can also significantly impact quality of life and survival. For MPS IVA, enzyme replacement therapy (ERT) with elosulfase alfa (Vimizim) was approved in 2014 and has been shown to improve endurance and respiratory function. Hematopoietic stem cell transplantation (HSCT) has been explored but its role remains less well-established compared to other MPS types. Surgical interventions, particularly cervical spine stabilization, are often necessary. There is currently no specific enzyme replacement therapy available for MPS IVB. Management for both subtypes includes multidisciplinary supportive care involving orthopedics, cardiology, ophthalmology, pulmonology, and audiology.

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