Diagnosis of the mucopolysaccharidoses

Abstract

The mucopolysaccharidoses (MPSs) often present a diagnostic challenge, particularly for patients who have more slowly progressive disease phenotypes, as early disease manifestations can be subtle or non-specific. However, certain types of bone and joint involvement should always prompt consideration of an MPS diagnosis, such as early joint involvement without classic inflammatory features or erosive bone lesions, claw hand, spinal deformities or dysostosis multiplex. All such patients should be referred to a geneticist or metabolic specialist for diagnostic evaluation. The earlier the diagnosis is made, the better the potential outcome of treatment. Each type of MPS is associated both with deficient activity of a specific lysosomal enzyme that degrades specific glycosaminoglycans (GAGs) and with abnormalities in urinary GAG excretion. MPS patients usually excrete excess GAG in urine and/or have different relative proportions of types of GAG in urine as compared with age-matched normal subjects. Although urinary GAG analyses (both quantitative and qualitative) can suggest the most likely type of MPS, diagnosis must be confirmed by enzyme assay. Multiple assays may be necessary to identify the disease subtype. Correct identification of the MPS type is essential to guide treatment and management decisions.

Systems biology study of mucopolysaccharidosis using a human metabolic reconstruction network

“…Currently, MPS diagnosis is based on the analysis (qualitative and quantitative) of GAG in biofluids (i.e., urine or plasma) and the measure of the enzymatic activity [5]. Nevertheless, different methodologies have been used to improve the specificity, sensitivity, and accuracy of GAG detection and differentiation.…”

“…However, difficult standardization, high costs, and the need of highly trained staff limit the access to these technologies [7]. In this sense, it is important to identify new biomarkers for disease prognosis, early diagnosis, and follow up of therapy efficacy [5,8]. New identified biomarkers include heparin cofactor IIthrombin complex, dipeptidyl peptidase IV, gangliosides GM2 and GM3, cholesterol, bis (monoacylglycero) phosphate, matrix metalloproteinases, TNF-α, chondroitin:dermatan sulfate ratio (DS/CS), interleukin (IL)-1β, are biomarkers obtained from research on humans and animal models [9,10].…”

Cribriform pattern in brain MRI: A diagnostic clue for mucopolysaccharidoses

“…1). Skeletal survey of the child revealed features suggestive of mucopolysaccharidosis 1H (Hurler syndrome), which was further confirmed by quantitative and qualitative urinary glycosoaminoglycan (GAG) analysis [1] revealing elevated levels of dermatan and heparan sulphate. …”

β-Glucuronidase, a Regulator of Lyme Arthritis Severity, Modulates Lysosomal Trafficking and MMP-9 Secretion in Response to Inflammatory Stimuli

“…BMDM were generated as described (19). BMDM growth medium consisted of RPMI 1640 medium (Invitrogen) supplemented with 30% L929 conditioned medium and 20% horse serum (HyClone).…”