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.