Diagnosing mucopolysaccharidosis IVA.
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.
Biochemical Genetics Laboratory, Greenwood Genetic Center, 106 Gregor Mendel Circle, Greenwood, SC 29646, USA. tim@ggc.org
Timothy C
TC
Wood
Katie
K
Harvey
Michael
M
Beck
Maira Graeff
MG
Burin
Yin-Hsiu
YH
Chien
Heather J
HJ
Church
Vânia
V
D'Almeida
Otto P
OP
van Diggelen
Michael
M
Fietz
Roberto
R
Giugliani
Paul
P
Harmatz
Sara M
SM
Hawley
Wuh-Liang
WL
Hwu
David
D
Ketteridge
Zoltan
Z
Lukacs
Nicole
N
Miller
Marzia
M
Pasquali
Andrea
A
Schenone
Jerry N
JN
Thompson
Karen
K
Tylee
Chunli
C
Yu
Christian J
CJ
Hendriksz
D000465:Algorithms; D005347:Fibroblasts / Q000201:enzymology; D006025:Glycosaminoglycans / Q000652:urine*; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D009081:Mucolipidoses / Q000175:diagnosis; D009085:Mucopolysaccharidosis IV / Q000175:diagnosis* / Q000201:enzymology* / Q000235:genetics / Q000652:urine; D052517:Multiple Sulfatase Deficiency Disease / Q000175:diagnosis; D009154:Mutation; D057089:Pathology, Molecular / Q000379:methods
D006025:Glycosaminoglycans