Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Mucopolysaccharidosis VII (MPS VII, Sly syndrome) is an autosomal recessive lysosomal storage disorder caused by the deficiency of beta-glucuronidase. The mucopolysaccharidoses are a group of disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of glycosaminoglycans (GAG). Accumulation of GAGs (previously called mucopolysaccharides) in lysosomes interferes with normal functioning of cells, tissues, and organs. MPS VII is caused by a reduced or absent activity of the beta-glucuronidase enzyme and gives rise to the physical manifestations of the disease.
Clinical features and severity of symptoms of MPS VII are widely variable ranging from severe lethal hydrops fetalis to more mild forms, which generally present at a later onset with a milder clinical presentation. In general, symptoms may include skeletal anomalies, coarse facies, hepatomegaly, neurological issues, and mental retardation. Treatment options may include bone marrow transplantation. Sly syndrome is 1 of the least common mucopolysaccharidoses with an incidence of 1 in 250,000 live births.
A diagnostic workup in an individual with MPS VII typically demonstrates elevated levels of urinary GAGs and increased amounts of dermatan sulfate, heparan sulfate, and chondroitin 6-sulfate detected on thin-layer chromatography. Reduced or absent activity of beta-glucuronidase in fibroblasts can confirm a diagnosis of MPS VII; however, enzymatic testing is not reliable to detect carriers. Molecular sequence analysis of the GUSB gene allows for detection of the disease-causing mutation in affected patients and subsequent carrier detection in relatives. Currently, no clear genotype-phenotype correlations have been established.
Detection of mucopolysaccharidosis type VII
Patients with mucopolysaccharidosis type VII (Sly syndrome) are deficient of beta glucuronidase.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Diagnosis of this lysosomal disorder is only available on fibroblasts. Carriers have not been reliably detected by this method.
-Lack of viable cells or bacterial contamination
-Failure to transport tissue in an appropriate media
-Excessive transport time,
-Exposure of the specimen to temperature extremes (freezing or >30 degrees C)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or =2.33 nmol/min/mg protein
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Neufeld EF, Muenzer J: The mucopolysaccharidoses. In The Metabolic and Molecular Basis of Inherited Disease. Vol 3. Eighth edition. Edited by CR Scriver, AL Beaudet, WS Sly, D Valle. New York, McGraw-Hill Book Company, 2001, pp 3421-3441