Interpretive Handbook

The mucopolysaccharidoses (MPSs) are a group of disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate (glycosaminoglycans; GAGs). Undegraded or partially degraded GAGs (also called mucopolysaccharides) are stored in lysosomes and excreted in the urine. Accumulation of GAGs in lysosomes interferes with normal functioning of cells, tissues, and organs resulting in the clinical features observed in MPS disorders. There are 11 known enzyme deficiencies that result in MPSs. In addition, abnormal GAG storage is observed in multiple sulfatase deficiency and in I-cell disease. Finally, an abnormal excretion of GAGs in urine is observed occasionally in other disorders including active bone diseases, connective tissue disease, hypothyroidism, urinary dysfunction, and oligosaccharidoses.

MPSs are autosomal recessive disorders with the exception of MPS II, which follows an X-linked inheritance pattern. Affected individuals typically experience a period of normal growth and development followed by progressive disease involvement encompassing multiple systems. The severity and features vary, and may include facial coarsening, organomegaly, skeletal changes, cardiac abnormalities, and developmental delays. Moreover, disease presentation varies from as early as late infancy to adulthood. Additional information regarding individual disorders can be found under test MPSSC/84464 Mucopolysaccharides (MPS) Screen, Urine.

A diagnostic workup for individuals with suspected MPS begins with Mayo Medical Laboratories' test MPSSC/84464 Mucopolysaccharides (MPS) Screen, Urine, which includes both the quantitative analysis of total GAGs and thin layer chromatography (TLC). Interpretation is based upon pattern recognition of the specific sulfate(s) detected on TLC and the qualitative analysis of their relative amounts of excretion. However, an abnormal MPS analysis is not sufficient to conclusively establish a specific diagnosis. It is strongly recommended to seek confirmation by an independent method, typically in vitro enzyme assay (available in either blood or cultured fibroblasts from a skin biopsy) and/or molecular analysis.

After a specific diagnosis has been established, Mayo Medical Laboratories' test MPSQN/81473 Mucopolysaccharides (MPS), Quantitative, Urine, which does not include the TLC, can be appropriate for monitoring the effectiveness of a bone marrow transplant or enzyme replacement therapy. However, some clinicians will opt to perform the MPS screen, which allows for monitoring of not only the total amount of GAGs, but also the excretion of specific sulfates, as these may change in patients with an MPS disorder undergoing treatment.

Monitoring patients with mucopolysaccharidosis who have had bone marrow transplants or are receiving enzyme therapy

An abnormally elevated excretion of glycosaminoglycan (GAG) is characteristic of mucopolysaccharidoses. GAG levels may normalize or remain elevated in patients who have undergone bone marrow transplants or are receiving enzyme replacement therapy.

Using this assay, a normal value for total glycosaminoglycan (GAG) can occasionally be obtained on a specimen that yielded a diagnostic thin-layer chromatography (TLC) pattern (ie, false negative). Conversely, an abnormal value for total GAG can occasionally be obtained on a specimen that yields a normal TLC pattern. This situation can occur as an artifact when a patient is treated with low-molecular-weight heparin. Other known causes are specimen contamination with acrylic polymers used in disposable diapers and several clinical situations associated with excessive connective tissue destruction, bladder disease, or bone disease.

0-4 months: < or =53.0 mg/mmol creatinine

5-18 months: < or =31.0 mg/mmol creatinine

19 months-2 years: < or =24.0 mg/mmol creatinine  

3-5 years: < or =16.0 mg/mmol creatinine

6-10 years: < or =12.0 mg/mmol creatinine

11-14 years: < or =10.0 mg/mmol creatinine

>14 years: < or =6.5 mg/mmol creatinine

Neufeld EF, Muenzer J: The mucopolysaccharidoses. In The Metabolic and Molecular Bases of Inherited Disease. Eighth edition. Edited by CR Scriver, AL Beaudet, D Valle, et al. New York, McGraw-Hill Book Company, 2001, pp 3421-3452