Morquio's Syndrome

Synonyms: Mucopolysaccharidosis type IVA (galactosamine-6-sulfatase deficiency); Mucopolysaccharidosis type IVB (beta galactosidase deficiency).

Affected children have normal intelligence and usually survive well into adulthood. Two forms are recognised:

• Type A: deficiency of the enzyme galactosamine-6-sulphatase causing faulty degradation of keratan sulphate with glycosaminoglycan deposits in the body tissues. Keratan sulphate is excreted in large amounts in urine.¹
• Type B: deficiency of the enzyme beta galactosidase. The phenotype is milder than in Type A.²

• The incidence is unknown but estimates have ranged from 1 case per 75,000 people in Northern Ireland to 1 case per 200,000 people in British Columbia.²
• Inheritance is as autosomal recessive trait.

Patients with Morquio syndrome appear healthy at birth. Often present with spinal deformity, growth retardation or genu valgus in the second or third year of life.

• Short stature (flat vertebrae cause a short trunk), short neck, moderate kyphosis or scoliosis, mild pectus carinatum (pigeon chest)
• Cervical spine: odontoid hypoplasia, atlantoaxial instability; may be associated with myelopathy with gradual loss of walking ability
• Joint laxity, mild dysostosis multiplex, dysplastic hips, large unstable knees and large elbows and wrists, flat feet
• The combined abnormalities usually result in a duck-waddling gait
• Mid-face hypoplasia and mandibular protrusion
• Thin teeth enamel
• Corneal clouding
• Mild hepatosplenomegaly

• Multiple epiphyseal dysplasia
• Other mucopolysaccharidoses

• Urine spot tests are readily available to screen for mucopolysaccharides but are associated with false-positive and false-negative results.
• Heparan, keratan, and dermatan sulphate can be distinguished by electrophoretic techniques to differentiate between the mucopolysaccharidoses.
• The diagnosis is confirmed by direct enzyme assay in leucocytes or fibroblasts.
• Prenatal diagnosis; enzyme activity can be measured in amniocytes or chorionic villi.
• Determination of the carrier state by enzyme analysis is not always possible because there is an overlap in enzyme activity between carriers and the normal population.
• Detection of gene mutations can be used in carrier testing.
• X-ray features of Morquio's disease include wide flaring of ilium, shallow acetabula, coxa valga and dysostosis multiplex.
• CT or MRI of the brain stem and cervical spine: to evaluate odontoid hypoplasia and cord compression.

• Treatment is currently only palliative.
• Possible future treatments include enzyme replacement, gene therapy and allogenic bone marrow transplantation.³

Surgical

• Some authorities recommend upper cervical spine fusion for all affected patients.
• Other potential operations include femoral osteotomies, corrective knee surgery, total hip replacement and total knee replacement.

• Atlantoaxial instability
• General anaesthesia may be particularly hazardous in view of managing a difficult airway as well as possible pulmonary and cardiac dysfunction
• Skeletal abnormalities may cause problems with mobility and pain
• Cervical myelopathy
• Obstructive sleep apnoea
• Pulmonary compromise (skeletal deformities) and are predisposed to chest infections (immobility)
• Valvular (aortic and mitral valve thickening) and coronary heart disease
• Hearing deficits
• Visual impairment: corneal clouding
• Dental caries (enamel abnormalities)

• Mental development is usually normal.
• Expected life-span is unimpaired but patients with severe features related to cervical instability may have a much shorter life expectancy.