Dataset Information

Diagnosing mucopolysaccharidosis IVA.

ABSTRACT: Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of biochemical genetics laboratory directors and clinicians involved in the diagnosis of MPS IVA, convened by BioMarin Pharmaceutical Inc., met to develop recommendations for diagnosis. The following conclusions were reached. Due to the wide variation and subtleties of radiographic findings, imaging of multiple body regions is recommended. Urinary glycosaminoglycan analysis is particularly problematic for MPS IVA and it is strongly recommended to proceed to enzyme activity testing even if urine appears normal when there is clinical suspicion of MPS IVA. Enzyme activity testing of GALNS is essential in diagnosing MPS IVA. Additional analyses to confirm sample integrity and rule out MPS IVB, multiple sulfatase deficiency, and mucolipidoses types II/III are critical as part of enzyme activity testing. Leukocytes or cultured dermal fibroblasts are strongly recommended for enzyme activity testing to confirm screening results. Molecular testing may also be used to confirm the diagnosis in many patients. However, two known or probable causative mutations may not be identified in all cases of MPS IVA. A diagnostic testing algorithm is presented which attempts to streamline this complex testing process.

SUBMITTER: Wood TC

PROVIDER: S-EPMC3590423 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Diagnosing mucopolysaccharidosis IVA.

Wood Timothy C TC Harvey Katie K Beck Michael M Burin Maira Graeff MG Chien Yin-Hsiu YH Church Heather J HJ D'Almeida Vânia V van Diggelen Otto P OP Fietz Michael M Giugliani Roberto R Harmatz Paul P Hawley Sara M SM Hwu Wuh-Liang WL Ketteridge David D Lukacs Zoltan Z Miller Nicole N Pasquali Marzia M Schenone Andrea A Thompson Jerry N JN Tylee Karen K Yu Chunli C Hendriksz Christian J CJ

Journal of inherited metabolic disease 20130201 2

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of biochemical genetics laboratory directors and clinicians involved in the diagnosis of MPS IVA, convened by BioMarin Pharmaceutical Inc., met to develop recommendations for diagnosis. Th ...[more]

PMID: 23371450

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Project description:Cardiovascular disease (CVD) in Mucopolysaccharidosis Type IVA (Morquio A), signified by valvular disease and cardiac hypertrophy, is the second leading cause of death and remains untouched by current therapies. Enzyme replacement therapy (ERT) is the gold-standard treatment for MPS disorders including Morquio A. Early administration of ERT improves outcomes of patients from childhood to adulthood while posing new challenges including prognosis of CVD and ERT's negligible effect on cardiovascular health. Thus, having accurate biomarkers for CVD could be critical. Here we show that cathepsin S (CTSS) and elastin (ELN) can be used as biomarkers of extracellular matrix remodeling in Morquio A disease. We found in a cohort of 54 treatment naïve Morquio A patients and 74 normal controls that CTSS shows promising attributes as a biomarker in young Morquio A children. On the other hand, ELN shows promising attributes as a biomarker in adolescent and adult Morquio A. Plasma/urine keratan sulfate (KS), and urinary glycosaminoglycan (GAG) levels were significantly higher in Morquio A patients (p < 0.001) which decreased with age of patients. CTSS levels did not correlate with patients' phenotypic severity but differed significantly between patients (median range 5.45-8.52 ng/mL) and normal controls (median range 9.61-15.9 ng/mL; p < 0.001). We also studied α -2-macroglobulin (A2M), C-reactive protein (CRP), and circulating vascular cell adhesion molecule-1 (sVCAM-1) in a subset of samples to understand the relation between ECM biomarkers and the severity of CVD in Morquio A patients. Our experiments revealed that CRP and sVCAM-1 levels were lower in Morquio A patients compared to normal controls. We also observed a strong inverse correlation between urine/plasma KS and CRP (p = 0.013 and p = 0.022, respectively) in Morquio A patients as well as a moderate correlation between sVCAM-1 and CTSS in Morquio A patients at all ages (p = 0.03). As the first study to date investigating CTSS and ELN levels in Morquio A patients and in the normal population, our results establish a starting point for more elaborate studies in larger populations to understand how CTSS and ELN levels correlate with Morquio A severity.

Dataset Information

Diagnosing mucopolysaccharidosis IVA.

Publications

Diagnosing mucopolysaccharidosis IVA.

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