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Morquio's syndrome

Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find one of our health articles more useful.

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

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What is Morquio's syndrome?1

Morquio's syndrome is an autosomal recessive lysosomal storage disorder caused by deficiency of either the enzyme N-acetyl-galactosamine-6-sulfate sulfatase (Morquio A) or enzyme beta-galactosidase (Morquio B).

It was first described in 1929 by Luis Morquio, a paediatrician from Uruguay, and James Brailsford, a radiologist from the UK. The division into type A and type B came about in 1976 when milder cases caused by a different enzyme deficiency were recognised.

Prior to this all cases were simply labelled as Morquio's syndrome and probably included both types. Although there can be clinical overlap, it is now recognised that the clinical features in type A and type B are substantially different.

Affected children have normal intelligence and usually survive well into adulthood. Two forms are recognised based on the enzyme deficiency:

  • Type A: deficiency of the enzyme galactosamine-6-sulfatase causing faulty degradation of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin sulfate (CS) which accumulate in various body tissues. KS is excreted in large amounts in urine.2

  • Type B: deficiency of the enzyme beta-galactosidase with accumulation of KS in various body tissues. The phenotype is milder than in type A.3

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.

There is remarkable genetic heterogeneity with 180 mutations described for the GALNS gene responsible for different levels of reduction in enzyme production. Likewise, several mutations have been described for GLB1 gene.

The majority of glycosaminoglycan such as KS is produced in the cartilage and therefore accumulated there, causing a direct impact on cartilage and bone development. This is responsible for the clinical presentation.

How common is Morquio's syndrome?(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.3

  • Inheritance is as autosomal recessive trait.

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Morquio's syndrome symptoms (presentation)4 5

Clinical features result because of deposition of GAGs in various tissues and reflect the pattern of deposition. Skeletal system is therefore most affected but there is also involvement of the visual system, auditory system, cardiovascular system and respiratory system.

Clinical manifestations of Morquio's syndrome type A vary from a severe form characterised by severe systemic bone dysplasia present at birth to a less severe form with less significant bone involvement diagnosed in adulthood.

In severely affected patients onset of the disease symptoms often occurs before 1 year of age and these cases are typically diagnosed before 5 years of age.

They commonly present with spinal deformity, there is growth restriction or genu valgus in the second or third year of life. Clinical manifestations include:

  • Short stature (flat vertebrae cause a short trunk), short neck, moderate kyphosis or scoliosis, and mild pectus carinatum (pigeon chest). Effect on height appears to be directly related to the severity of disease with the final height being less than 120 cm in severe cases. Very mild cases may have near normal height.

  • 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 affecting vision.

  • Recurrent upper airway infections and hearing problems.

  • Mild hepatosplenomegaly.

The international registry for Morquio A is an excellent source of information regarding clinical manifestations and outcomes of patients with Morquio's syndrome type A.6

Clinical manifestations of type B are distinct from type A with normal or near normal stature, with normal neck development and absence of hearing loss and hepatomegaly. Clinical manifestations include:

  • Platyspondyly of vertebrae.

  • Dysplasia of the long bones.

  • Atlanto-occipital instability.

  • Genu valgum.

  • Gait abnormalities.

  • Corneal clouding.

Differential diagnosis

  • Multiple epiphyseal dysplasia.

  • Other mucopolysaccharidoses.

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  • Once there is clinical suspicion of the diagnosis, biochemical testing is indicated

  • The conventional approach is to test for total urine GAGs and if that is positive to proceed to measurement of GALNS enzyme activity. However, urine tests are screening tests and can be falsely negative; current recommendation is to carry out enzymatic or molecular testing to confirm or rule out diagnosis of Morquio's syndrome.

  • Quantitative measurement of urine GAGs identifies elevation of urinary GAGs and can be used to screen for any mucopolysaccharidosis. Qualitative measurement identifies elevation of specific GAGs and helps in the differential diagnosis of various mucopolysaccharidoses. The positive identification of KS is generally specific for Morquio syndrome.

  • Enzyme activity testing is essential for diagnosis of Morquio's syndrome. Leukocytes or cultured dermal fibroblasts are strongly recommended for enzyme activity testing to confirm screening results.

  • Molecular testing may also be used to confirm diagnosis in many patients. However, two known or probable causative mutations may not be identified in all cases of Morquio's syndrome.

  • In all suspected cases of Morquio's syndrome radiological evaluation should be carried out as part of the diagnostic process. As radiological findings can be variable, it is recommended to carry out a skeletal survey which allows evaluation of various parts of the body including the skull, spine, hips and limbs.

  • Radiological findings in Morquio's syndrome include odontoid hypoplasia, atlanto-axial subluxation, flared ribs, short thorax, flattened capital femoral epiphyses, coxa valga, universal platyspondyly, anterior beaking of vertebrae and short ulna.

  • CT or MRI scanning of the brainstem and cervical spine is useful in evaluation of odontoid hypoplasia and early identification of spinal cord compression (SCC).

  • 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.

Morquio's syndrome treatment and management8

  • Patients with Morquio's syndrome and their families need individualised multidisciplinary management. This includes genetic counselling, supportive therapies, physiotherapy and orthopaedic interventions.

  • Orthopaedic surgical procedures performed by a well-trained team improve quality of life, prevent complications and can enhance survival. These include:

    • Decompression and fusion of the upper cervical spine - required to treat instability and spinal cord compression.

    • Hip joint problems lead to progressive difficulty in walking, with many children becoming wheelchair-bound by their teens. Surgery (eg, femoral osteotomy) is often needed in these patients to preserve the hip joint. Joint replacement surgery may be needed in adults with severe arthritis and pain.

  • Enzyme replacement therapy and haematopoietic stem cell transplantation are available for patients with MPS IVA, but neither has enough impact on bone and cartilage lesions.9


  • 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.

  • Spinal cord compression and cervical myelopathy.

  • Obstructive sleep apnoea.

  • Pulmonary compromise (skeletal deformities) and 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).


  • The age at diagnosis, natural progression of the disease, and severity of symptoms are determined by severity of disease, which may be associated with specific genetic mutations.

  • Mental development is usually normal, as the central nervous system is usually spared.

  • Patients with a severe form of the disease often do not survive beyond the second or third decade of life, due to cervical instability and pulmonary compromise.

  • Survival to adulthood is common and in patients with less severe symptoms, life expectancy can be normal.

  • Less severely affected females have given birth to children, although delivery is always by caesarean section.

Further reading and references

  1. Zanetti A, D'Avanzo F, AlSayed M, et al; Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome): A review and classification of GALNS gene variants and reporting of 68 novel variants. Hum Mutat. 2021 Nov;42(11):1384-1398. doi: 10.1002/humu.24270. Epub 2021 Aug 23.
  2. Mucopolysaccharidosis Type IVa, MPS4A - Morquio Syndrome A; Online Mendelian Inheritance in Man (OMIM)
  3. Mucopolysaccharidosis Type IVb - Morquio Syndrome B (beta-galactosidase deficiency); Online Mendelian Inheritance in Man (OMIM)
  4. Hendriksz CJ, Harmatz P, Beck M, et al; Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. Mol Genet Metab. 2013 Sep-Oct;110(1-2):54-64. doi: 10.1016/j.ymgme.2013.04.002. Epub 2013 Apr 10.
  5. Khan SA, Peracha H, Ballhausen D, et al; Epidemiology of mucopolysaccharidoses. Mol Genet Metab. 2017 Jul;121(3):227-240. doi: 10.1016/j.ymgme.2017.05.016. Epub 2017 May 26.
  6. Montano AM, Tomatsu S, Gottesman GS, et al; International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. J Inherit Metab Dis. 2007 Apr;30(2):165-74. Epub 2007 Mar 8.
  7. Wood TC, Harvey K, Beck M, et al; Diagnosing mucopolysaccharidosis IVA. J Inherit Metab Dis. 2013 Mar;36(2):293-307. doi: 10.1007/s10545-013-9587-1. Epub 2013 Feb 1.
  8. Tomatsu S, Yasuda E, Patel P, et al; Morquio A syndrome: diagnosis and current and future therapies. Pediatr Endocrinol Rev. 2014 Sep;12 Suppl 1:141-51.
  9. Sawamoto K, Alvarez Gonzalez JV, Piechnik M, et al; Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management. Int J Mol Sci. 2020 Feb 23;21(4):1517. doi: 10.3390/ijms21041517.

Article History

The information on this page is written and peer reviewed by qualified clinicians.

  • Next review due: 19 Aug 2028
  • 21 Aug 2023 | Latest version

    Last updated by

    Dr Colin Tidy, MRCGP

    Peer reviewed by

    Dr Pippa Vincent, MRCGP
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