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Morquio A Syndrome (MPS IVA)

Morquio A syndrome is a progressive disease affecting many body systems, with debilitating manifestations including skeletal abnormalities, vision and hearing loss, and cardiac and respiratory impairment.1

What is Morquio A Syndrome?

Morquio A syndrome is one of a group of rare, inherited metabolic disorders known as the mucopolysaccharidoses (MPS), which have an overall prevalence of around 1 in 25,000 births.2,3 MPS diseases are lysosomal storage disorders that arise because of deficiencies in the various enzymes that break down glycosaminoglycans (GAGs), a type of carbohydrate.2 Morquio A syndrome is caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase (GALNS).2 The progressive accumulation of GAGs in various tissues in people with Morquio A syndrome affects many body systems and leads to serious health problems.4 The condition causes respiratory, cardiac, musculoskeletal and sensory impairments, which can result in diminished functional capacity and independence, impaired quality of life and early death.2,4,5

Morquio A is an autosomal recessive disease,2 which means that if both parents are carriers of the abnormal GALNS gene, each time they have a child, there is a one in four chance of that child having Morquio A syndrome.

Symptoms of Morquio A Syndrome

The symptoms, severity and progression of Morquio A syndrome vary widely between patients.1 Infants with Morquio A syndrome usually appear healthy at birth.1 However, over time, patients progressively develop serious skeletal and joint abnormalities and a range of other manifestations such as airway obstruction, spinal cord compression, heart valve disease, corneal clouding, hearing loss and dental problems.1 Short stature and skeletal dysplasia occur in most patients, and bone deformity is often one of the first signs of the condition.4 The symptoms of Morquio A syndrome mean patients experience significant functional limitations and reduced quality of life, with exercise and respiratory capacity limitations becoming more severe with age.6 People with Morquio A syndrome have normal intelligence and adult patients often work while they are physically able.5 However, the manifestations and deteriorating mobility caused by Morquio A syndrome can make normal life difficult for patients and affect everyday activities such as attendance at school or work and social activities.5

Diagnosing Morquio A Syndrome3

Once suspected, MPS is usually diagnosed through biochemical or molecular genetic testing, however, early clinical recognition of the condition is challenging because of its rarity and the varied and sometimes subtle nature of early signs and symptoms. Substantial diagnostic delays are common in MPS. The typical delay from the onset of symptoms to diagnosis is around three years (ranging from 0 to 38 years). Patients may present to an array of medical specialties, including orthopaedics, cardiology, neurology, rheumatology, paediatrics and general medicine. Diagnostic delays often involve referrals from one physician to another and place a substantial burden on the patient and caregivers. Earlier recognition allows for prompt initiation of treatment (when available) and management of secondary complications, as well as enabling families to benefit from support and counselling.

Managing Morquio A Syndrome

A multidisciplinary team is required to manage the diverse range of disease manifestations in patients with Morquio A syndrome.2 Guidelines recommend patients should be regularly monitored so that timely interventions can be made to help avoid irreversible damage caused by the natural history of Morquio A syndrome, to manage disease manifestations and to maintain patients’ quality of life.2 This may include addressing clinical signs and symptoms through medication, surgery and physical therapy, as well as disease-modifying treatment.1,2


References
  1. Hendriksz CJ et al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet 2015;167A(1):11-25.
  2. Akyol MU et al. Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance. Orphanet J Rare Dis 2019;14:137.
  3. Clarke L et al. Understanding the early presentation of mucopolysaccharidoses disorders: Results of a systematic literature review and physician survey. J Inborn Errors Metab Screen 2018;6:1-12.
  4. Lavery C and Hendriksz C. Mortality in patients with Morquio Syndrome A. JIMD Rep 2015;15:59-66.
  5. Hendriksz CJ et al. Burden of disease in patients with Morquio A syndrome: results from an international patient-reported outcomes survey. Orphanet J Rare Dis 2014;9:32.
  6. Harmatz P et al. The Morquio A Clinical Assessment Program: Baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects. Mol Genet Metab 2013;109(1):54-61.