International guidelines for the management and treatment of Morquio A syndrome

Abstract

Morquio A syndrome (mucopolysaccharidosis IVA) is a lysosomal storage disorder associated with skeletal and joint abnormalities and significant non-skeletal manifestations including respiratory disease, spinal cord compression, cardiac disease, impaired vision, hearing loss, and dental problems. The clinical presentation, onset, severity and progression rate of clinical manifestations of Morquio A syndrome vary widely between patients. Because of the heterogeneous and progressive nature of the disease, the management of patients with Morquio A syndrome is challenging and requires a multidisciplinary approach, involving an array of specialists. The current paper presents international guidelines for the evaluation, treatment and symptom-based management of Morquio A syndrome. These guidelines were developed during two expert meetings by an international panel of specialists in pediatrics, genetics, orthopedics, pulmonology, cardiology, and anesthesia with extensive experience in managing Morquio A syndrome.

Keywords: diagnosis; disease management; guidelines; mucopolysaccharidosis IV; symptom assessment.

FIG. 1

Typical appearance of patients with Morquio A syndrome, showing short stature with short neck and profound skeletal and joint abnormalities (left) and a patient with a non-classical phenotype of Morquio A syndrome showing normal stature (right).

FIG. 2

Diagnostic algorithm for Morquio A syndrome. Adapted from Wood TC et al. [Wood et al., 2013]. DBS: dried blood spot.

FIG. 3

Typical radiographic features (dysostosis multiplex) in patients with Morquio A syndrome: (A) Rib cage from a 12 year-old female Morquio A patient showing paddle shaped ribs. (B) Typical dysostosis multiplex changes in the pelvis and hips of an 8 year-old Morquio A patient showing dysplastic femoral epiphyses and narrowed inferior ilia sloping into the acetabular roofs. (C) Knee valgus in a 7 year-old Morquio A patient. Reproduced from Dhawale et al. [Dhawale et al., 2012] with permission from Lippincott Williams & Wilkins. (D) Cervical spine showing dens hypoplasia, which may be associated with atlantoaxial instability. Reproduced from Solanki et al. [Solanki et al., 2013] with permission from Springer. (E) Thoracolumbar spine changes including platyspondyly, anterior beaking, thoracolumbar kyphosis, and posterior vertebral scalloping. Reproduced from Solanki et al. [Solanki et al., 2013] with permission from Springer.

FIG. 4

GAG deposits within walls of the upper airway of a patient with Morquio A causing narrowing of the pharynx and larynx.

FIG. 5

Pediatric (top) and adult (bottom) teeth of patients with Morquio A showing widely spaced teeth, pointed cusps and spade-shaped incisors.