Mucopolysaccharidosis type IVA (
MPS IVA) is a
lysosomal storage disease caused by mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. Skeletal dysplasia and the related clinical features of
MPS IVA are caused by disruption of the cartilage and its extracellular matrix, leading to a growth imbalance.
Enzyme replacement therapy (ERT) with recombinant human GALNS has yielded positive results in activity of daily living and endurance tests. However, no data have demonstrated improvements in bone lesions and bone grow thin
MPS IVA after ERT, and there is no correlation between therapeutic efficacy and urine levels of
keratan sulfate, which accumulates in
MPS IVA patients. Using qualitative and quantitative proteomics approaches, we analyzed leukocyte samples from healthy controls (n = 6) and from untreated (n = 5) and ERT-treated (n = 8, sampled before and
after treatment)
MPS IVA patients to identify potential
biomarkers of disease. Out of 690
proteins identified in leukocytes, we selected a group of
proteins that were dysregulated in
MPS IVA patients with ERT. From these, we identified four potential
protein biomarkers, all of which may influence bone and cartilage metabolism:
lactotransferrin,
coronin 1A,
neutral alpha-glucosidase AB, and
vitronectin. Further studies of cartilage and bone alterations in
MPS IVA will be required to verify the validity of these
proteins as potential
biomarkers of
MPS IVA.