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Diagnosing mucopolysaccharidosis IVA
Author(s) -
Wood Timothy C.,
Harvey Katie,
Beck Michael,
Burin Maira Graeff,
Chien YinHsiu,
Church Heather J.,
D'Almeida Vânia,
Diggelen Otto P.,
Fietz Michael,
Giugliani Roberto,
Harmatz Paul,
Hawley Sara M.,
Hwu WuhLiang,
Ketteridge David,
Lukacs Zoltan,
Miller Nicole,
Pasquali Marzia,
Sche Andrea,
Thompson Jerry N.,
Tylee Karen,
Yu Chunli,
Hendriksz Christian J.
Publication year - 2013
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-013-9587-1
Subject(s) - mucopolysaccharidosis , hunter syndrome , medicine , enzyme replacement therapy , sulfatase , mucopolysaccharidosis i , pathology , enzyme , disease , biochemistry , biology
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.