Review of clinical presentation and diagnosis of 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.

https://link.springer.com/content/pdf/10.1007%2Fs10545-013-9587-1.pdf

Diagnosing mucopolysaccharidosis IVA

https://europepmc.org/articles/PMC5293636?pdf=render

Mucopolysaccharidosis IVA and glycosaminoglycans.

Mucopolysaccharidosis type IVA (MPS IVA, or Morquio syndrome type A) is an inherited metabolic lysosomal disease caused by the deficiency of the N-acetylglucosamine-6-sulfate sulfatase enzyme. The deficiency of this enzyme accumulates the specific glycosaminoglycans (GAG), keratan sulfate, and chondroitin-6-sulfate mainly in bone, cartilage, and its extracellular matrix. GAG accumulation in these lesions leads to unique skeletal dysplasia in MPS IVA patients. Clinical, radiographic, and biochemical tests are needed to complete the diagnosis of MPS IVA since some clinical characteristics in MPS IVA are overlapped with other disorders. Early and accurate diagnosis is vital to optimizing patient management, which provides a better quality of life and prolonged life-time in MPS IVA patients. Currently, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are available for patients with MPS IVA. However, ERT and HSCT do not have enough impact on bone and cartilage lesions in patients with MPS IVA. Penetrating the deficient enzyme into an avascular lesion remains an unmet challenge, and several innovative therapies are under development in a preclinical study. In this review article, we comprehensively describe the current diagnosis, treatment, and management for MPS IVA. We also illustrate developing future therapies focused on the improvement of skeletal dysplasia in MPS IVA.

/pdf/mucopolysaccharidosis-iva-diagnosis-treatment-and-management-5e4gwzcwqw.pdf

Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management

Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations

textA new fluorogenic substrate, 4 methylumbelliferyl B-D-6-sulphogalactoside, was used for the
assay of galactose-6-sulphate sulphatase activity in chorionic villi, cultured villus cells, and
amniocytes. The fluorometric assay is much more convenient than the conventional assay
using radiolabelled, sulphated oligosaccharides. Both types of substrate were used in the
prenatal diagnosis of three pregnancies at risk for Morquio type A disease using amniocytes.
These enzyme tests, as well as electrophoresis of glycosaminoglycans in the amniotic fluid,
indicated affected fetuses in two pregnancies and a non-affected fetus in one.

/pdf/prenatal-diagnosis-of-morquio-disease-type-a-using-a-simple-574oep85k8.pdf

J. Huumans

Papers

Prenatal diagnosis of morquio disease type a using a simple fluorometric enzyme assay