Mucopolysaccharidosis Type IV

Mucopolysaccharidosis type IV (Morquio syndrome) is an autosomal recessive skeletal dysplasia due to deficiency of N-acetylgalactosamine-6-sulfatase (type A, GALNS) or beta galactosidase (type B, GLB1), with storage of keratan sulphate and chondroitin-6-sulphate. Intelligence is normal, but skeletal disease threatens the cervical spinal cord, airway and mobility.

Pathophysiology. Keratan sulphate accumulates in cartilage and bone, where it disrupts chondrocyte function and endochondral ossification. Type B shares its gene with GM1 gangliosidosis but causes only skeletal disease.

Odontoid hypoplasia and ligamentous laxity cause atlantoaxial instability.

Enzyme replacement therapy is available for type A.

• Short trunk dwarfism with severe growth failure, and pectus carinatum
• Kyphoscoliosis, genu valgum, and joint laxity with limited extension
• Odontoid hypoplasia with atlantoaxial instability, and cervical cord compression
• Hip dysplasia and early degenerative joint disease
• Corneal clouding, and hearing loss
• Aortic and mitral valve disease
• Tracheal narrowing and restrictive lung disease, with sleep apnoea
• Dental enamel abnormalities, with caries
• Hepatomegaly in some
• Normal intelligence
• Attenuated forms: milder skeletal disease with later presentation

• Urine keratan sulphate: raised, although levels fall with age and may be normal in attenuated forms.
• Enzyme assay for GALNS (type A) or beta galactosidase (type B) in leukocytes or fibroblasts.
• GALNS and GLB1 sequencing, with deletion and duplication analysis.
• Skeletal survey with spine imaging; flexion extension cervical views and MRI of the craniocervical junction.
• Echocardiography, pulmonary function tests and sleep study.
• Ophthalmology, audiology and hip imaging.

• Enzyme replacement therapy for type A: elosulfase alfa 2 mg/kg intravenously once weekly as an infusion. Premedicate with an antihistamine (cetirizine 10 mg orally; children 1 to 5 years 2.5 mg twice daily, 6 to 11 years 5 mg twice daily) 30 to 60 minutes before the infusion. Keep adrenaline 0.5 mg intramuscularly (children 0.01 mg/kg, maximum 0.5 mg) available because anaphylaxis occurs.
• Cervical spine: fusion of C1 to C2 or occiput to C2 for instability or myelopathy. Use a neck brace and avoid hyperflexion. Monitor with neurophysiology during anaesthesia.
• Anaesthesia: specialist airway planning because intubation can be difficult, with risk of cord injury from neck movement.
• Skeletal surgery: growth modulation by hemiepiphysiodesis or osteotomy for genu valgum, hip surgery, and spinal surgery for progressive kyphoscoliosis.
• Respiratory care: sleep study and continuous positive airway pressure for obstructive apnoea, and tracheal assessment.
• Cardiac care: yearly echocardiography, with valve replacement for severe disease.
• Eye and hearing care: correction of refractive error, corneal transplant for severe clouding, and hearing aids.
• Pain and function: paracetamol 1 g up to four times daily (maximum 4 g), physiotherapy and mobility aids.
• Dental care: early dental review.
• Genetic counselling: a 25% recurrence risk in each pregnancy, with prenatal diagnosis available.

Special groups.

• Any anaesthetic: arrange cervical spine imaging and specialist anaesthesia first.

Monitoring. Cervical spine imaging yearly, and neurological examination at each visit. Echocardiography, pulmonary function and sleep study yearly, and eye and hearing review yearly.

Referral and escalation. Refer to clinical genetics, metabolic medicine, orthopaedics and spinal surgery. Emergency for new limb weakness, bladder dysfunction, neck pain with neurological signs or airway compromise.