Skip to main content
SpringerLink
Log in

Intellectual and neurological functioning in Morquio syndrome (MPS IVa)

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Mucopolysaccharidosis type IVa (MPS IVa, Morquio syndrome OMIM #253000) is a lysosomal storage disease caused by deficiency in N-acetylgalactosamine-6-sulfatase (GALNS, EC 3.1.6.4; encoded by GALNS gene at 16q24.3). Unlike other MPS disorders involving excessive heparan and dermatan sulfate, Morquio syndrome has not been associated with neurological involvement nor with intellectual impairment as this disorder of keratan sulfate has been described as a purely visceral and skeletal disorder. Neurocognitive assessment was undertaken of MPS IVa patients with age appropriate intellectual tests as well as a Child Behaviour Checklist as part of clinical follow up. Available neuroimaging studies (MRI and MR spectroscopy) were reviewed. Whilst more than half of the overall IQ scores fell in the average range, scores for 3/8 children fell below average. A number of behavioural problems were highlighted, including anxiety/depression, attention and somatic complaints. Subtle neuroimaging abnormalities were demonstrated in over half of the children. These findings present a challenge to existing assumptions about the nature of Morquio A syndrome. A hypothesis regarding the potential role of calcium signalling is explored.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Capitao L, Sampaio A et al. (2011) Williams syndrome hypersociability: a neuropsychological study of the amygdala and prefrontal cortex hypotheses. Res Dev Disabil 32(3):1169–1179

    Article  PubMed  Google Scholar 

  • Davison JE, Hendriksz CJ et al. (2010) Quantitative in vivo brain magnetic resonance spectroscopic monitoring of neurological involvement in mucopolysaccharidosis type II (Hunter Syndrome). J Inherit Metab Dis 33(6):819

    Google Scholar 

  • Davison JE, Davies NP et al. (2011) MR spectroscopy-based brain metabolite profiling in propionic acidaemia: metabolic changes in the basal ganglia during acute decompensation and effect of liver transplantation. Orphanet J Rare Dis 6(1):19

    Article  PubMed  Google Scholar 

  • Dvorak-Ewell M, Wendt D et al. (2011) "Enzyme replacement in a human model of mucopolysaccharidosis IVA in vitro and its biodistribution in the cartilage of wild type mice.". PLoS ONE [Electron Resour] 5(8):e12194

    Article  Google Scholar 

  • Eisengart, J and Delaney K (2011) Age and Cognitive/adaptive function in MPS IIIA (Sanfilippo syndrome). 7th Annual World Symposium, Lysosomdal disease network

  • Gargus JJ (2010) Mitochondrial component of calcium signalling abnormality in autism. Autism: oxidative stress, inflammation and immune abnormalities. Chauhan A, Chauhan V and Brown T, CRC Press: 209–226

  • Holt JB, Poe MD et al. (2011) Natural progression of neurological disease in mucopolysaccharidosis type II. Pediatrics 127(5):e1258–e1265

    Article  PubMed  Google Scholar 

  • Jawaid A, Schmolck H et al. (2008) Hypersociability in Williams syndrome: a role for the amygdala? Cogn Neuropsychiatry 13(4):338–342

    Article  PubMed  Google Scholar 

  • Jones W, Bellugi U et al. (2000) "II. Hypersociability in Williams Syndrome.". J Cogn Neurosci 12(Suppl 1):30–46

    Article  PubMed  Google Scholar 

  • Kantarci K, Jack CR et al. (2000) Regional metabolic patterns in mild cognitive impairment and Alzheimer’s disease: A 1H MRS study. Neurology 55(2):210–217

    Article  PubMed  CAS  Google Scholar 

  • Koto A, Horwitz AL et al. (1978) The morquio syndrome: Neuropathology and biochemistry. Ann Neurol 4(1):26–36

    Article  PubMed  CAS  Google Scholar 

  • Kumar YV, Narayanan HS et al. (1979) A report of two cases of Morquio’s syndrome associated with mental retardation. Aust J Ment Retard 5(8):319–321

    Google Scholar 

  • Lloyd-Evans E, Platt FM (2011) Lysosomal Ca(2+) homeostasis: role in pathogenesis of lysosomal storage diseases. Cell Calcium 50(2):200–205

    Article  PubMed  CAS  Google Scholar 

  • Miller B, Sheppard AM et al. (1997) Developmental expression of keratan sulfate-like immunoreactivity distinguishes thalamic nuclei and cortical domains. J Comp Neurol 380(4):533–552

    Article  PubMed  CAS  Google Scholar 

  • Montaño AM, Yamagishi A et al. (2000) "The mouse N-acetylgalactosamine-6-sulfate sulfatase (Galns) gene: cDNA isolation, genomic characterization, chromosomal assignment and analysis of the 5′-flanking region.". Biochimica et Biophysica Acta (BBA) - Mol Basis Dis 1500(3):323–334

    Article  Google Scholar 

  • Northover H, Cowie RA et al. (1996) Mucopolysaccharidosis type IVA (Morquio syndrome): a clinical review. J Inherit Metab Dis 19(3):357–365

    Article  PubMed  CAS  Google Scholar 

  • Ong DS, Mu TW et al. (2010) Endoplasmic reticulum Ca2+ increases enhance mutant glucocerebrosidase proteostasis. Nat Chem Biol 6(6):424–432

    Article  PubMed  CAS  Google Scholar 

  • Potegal, M and Yund B (2011) Comparison of social/emotional function in children with MPS I and MPS III: Interim Report. 7th Annual World Symposium, Lysosomdal disease network

  • Sasaki T, Garant PR (1986) Ultracytochemical demonstration of ATP-dependent calcium pump in ameloblasts of rat incisor enamel organ. Calcif Tissue Int 39(2):86–96

    Article  PubMed  CAS  Google Scholar 

  • Sasaki T, Garant PR (1987) Calmodulin blocker inhibits Ca++ − ATPase activity in secretory ameloblast of rat incisor. Cell Tissue Res 248(1):103–110

    Article  PubMed  CAS  Google Scholar 

  • Singh J, Di Ferrante N et al. (1976) N-acetylgalactosamine-6-sulfate sulfatase in man. Absence of the enzyme in Morquio disease. J Clin Invest 57(4):1036–1040

    Article  PubMed  CAS  Google Scholar 

  • Tessitore A, Pirozzi M et al. (2009) Abnormal autophagy, ubiquitination, inflammation and apoptosis are dependent upon lysosomal storage and are useful biomarkers of mucopolysaccharidosis VI. Pathogenetics 2(1):4

    Article  PubMed  Google Scholar 

  • Tomatsu S, Orii KO et al. (2003) Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns−/−) produced by targeted disruption of the gene defective in Morquio A disease. Hum Mol Genet 12(24):3349–3358

    Article  PubMed  CAS  Google Scholar 

  • Tomatsu S, Montano AM et al. (2008) Enzyme replacement therapy in a murine model of Morquio A syndrome. Hum Mol Genet 17(6):815–824

    Article  PubMed  CAS  Google Scholar 

  • Vicencio JM, Lavandero S et al. (2010) Ca2+, autophagy and protein degradation: thrown off balance in neurodegenerative disease. Cell Calcium 47(2):112–121

    Article  PubMed  CAS  Google Scholar 

  • Vitner EB, Platt FM et al. (2010) Common and uncommon pathogenic cascades in lysosomal storage diseases. J Biol Chem 285(27):20423–20427

    Article  PubMed  CAS  Google Scholar 

  • Wang F, Agnello G et al. (2011) "Ca2+ homeostasis modulation enhances the amenability of L444P glucosylcerebrosidase to proteostasis regulation in patient-derived fibroblasts.". ACS Chem Biol [Electron Resour] 6(2):158–168

    Article  CAS  Google Scholar 

  • Zhang H, Uchimura K et al. (2006) Brain keratan sulfate and glial scar formation. Ann N Y Acad Sci 1086:81–90

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements and disclosures

“JED funded by Clinical Research Training Fellowship from Sparks: The Children’s Medical Research Charity.”

CJH is the Chief Investigator for the phase 1/ 2 clinical trial on the use of BMN110 in children affected by MPS Iva sponsored by Biomarin Therapeutical Inc. He has a consulting agreement with Biomarin Therapeutical Inc. and has received honoraria and research funds from the sponsor but not relating to this paper.

Author information

Authors and Affiliations

  1. School of Clinical & Experimental Medicine, University of Birmingham, Birmingham, UK

    J. E. Davison

  2. Clinical Psychology, Birmingham Children’s Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham, UK

    S. Kearney & J. Horton

  3. Paediatric Radiology, Birmingham Children’s Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham, UK

    K. Foster

  4. Cancer Sciences, University of Birmingham, Birmingham, UK

    A. C. Peet

  5. Inherited Metabolic Disorders Department, Birmingham Children’s Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham, B4 6NH, UK

    J. E. Davison & C. J. Hendriksz

  6. Paediatric Oncology, Birmingham Children’s Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham, UK

    A. C. Peet

Authors
  1. J. E. Davison
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Kearney
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Horton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Foster
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. C. Peet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. J. Hendriksz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. J. Hendriksz.

Additional information

Communicated by: Gregory M. Pastores

Competing interest: None declared

Rights and permissions

Reprints and permissions

About this article

Cite this article

Davison, J.E., Kearney, S., Horton, J. et al. Intellectual and neurological functioning in Morquio syndrome (MPS IVa). J Inherit Metab Dis 36, 323–328 (2013). https://doi.org/10.1007/s10545-011-9430-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10545-011-9430-5

Keywords

Search

Navigation