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-sulfatase causing faulty degradation of keratan sulfate (KS) with glycosaminoglycan (GAG) deposits in the body tissues. Keratan sulfate 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

A genetic defect has been identified in the N-acetyl-galactosamine-6-sulfate sulfatase (GALNS gene) in Morquio's syndrome type IVA or beta-galactosidase (GLB1 gene) in Morquio's syndrome type IVB. The catabolism of chondroitin 6-sulfate is also affected by the GALNS gene defect,³

Epidemiology

• 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.

Presentation

Patients with Morquio's syndrome appear healthy at birth. They often present with spinal deformity, there is 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, atlanto-axial instability; may be associated with myelopathy with gradual loss of walking ability
• Joint laxity, mild dysostosis multiplex, dysplastic hips, large unstable knees, large elbows and wrists, and 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

Differential diagnosis

• Multiple epiphyseal dysplasia
• Other mucopolysaccharidoses

Investigations

• Urine spot tests are readily available to screen for mucopolysaccharides but are associated with false-positive and false-negative results.
• Heparan, keratan and dermatan sulfate can be distinguished by electrophoretic techniques to differentiate between the mucopolysaccharidoses.
• A new ELISA test is available to quantify keratan sulfate levels in the urine and blood of patients with Morquio's syndrome type IVA.
• 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 although the tests are not always accurate.
• X-ray features of Morquio's syndrome include wide flaring of the ilium, shallow acetabula, coxa valga and dysostosis multiplex.
• CT or MRI scanning of the brain stem and cervical spine: to evaluate odontoid hypoplasia and cord compression.

Management

• 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.

Complications

• Atlanto-axial 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 predisposition to chest infections (immobility)
• Valvular (aortic and mitral valve thickening) and coronary heart disease
• Hearing deficits
• Visual impairment: corneal clouding
• Dental caries (enamel abnormalities)

Prognosis

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

Document references

1. Morquio syndrome A, Online Mendelian Inheritance in Man (OMIM)
2. Morquio's disease type B (beta-galactosidase deficiency), Online Mendelian Inheritance in Man (OMIM)
3. Braverman N; Mucopolysaccharidosis Type IV. eMedicine.com,2009.

Internet and further reading

• The International Morquio Support Group

Acknowledgements