Test Catalog

Test ID: LYSDU    
Lysosomal Storage Disorders Screen, Urine

Useful For Suggests clinical disorders or settings where the test may be helpful

Screening patients suspected of having a lysosomal storage disorder

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This is a general urine screening test for a broad array of lysosomal storage (LSD) and related disorders. Not all LSDs are detectable by this method.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

A combined analysis and interpretation is reported to the client.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Lysosomal storage disorders (LSD) are a diverse group of inherited diseases characterized by the intracellular accumulation of macromolecules leading to cell damage and organ dysfunction. Approximately 50 lysosomal storage disorders have been described with a wide phenotypic spectrum and ranging in severity from neonatal lethal to later onset milder variants.

 

Although classification is not always straightforward, LSDs are generally categorized according to the type of storage material that accumulates in the cells and tissues. Major categories include mucopolysaccharidoses, oligosaccharidoses, mucolipidoses, and sphingolipidoses. In many cases, accumulating analytes can be detected in urine. Screening for these disorders typically begins with an analysis to detect disease-specific metabolite patterns or profiles indicative of a LSD. The combined analysis of disease-specific markers for LSDs in multiple tests can allow for the identification of additional disorders that may not be picked up using any of the single tests alone. 

 

Disorders detectable by this approach include the oligosaccharidoses alpha-mannosidosis, aspartylglucosaminuria, fucosidosis, Schindler disease, and sialidosis; the sphingolipidoses GM1 gangliosidosis, Sandhoff disease, galactosialidosis, saposin B deficiency, metachromatic leukodystrophy, multiple sulfatase deficiency, Fabry disease, Gaucher disease, and Krabbe disease; the mucopolysaccharidoses excluding MPS IX (hyaluronidase deficiency); the glycogen storage disorder Pompe disease and the mucolipidoses types II and III. Additionally, other disorders such as CDG type IIb, and de-glycosylation disorders such as NGLY1-CDG may also be detected.

 

The mucopolysaccharidoses (MPS) are a subset of lysosomal storage disorders caused by the deficiency of any one 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 MPS. 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.

 

The oligosaccharidoses (glycoproteinoses) are a subset of lysosomal storage disorders caused by the deficiency of any one of the lysosomal enzymes involved in the degradation of complex oligosaccharide chains. They are characterized by the abnormal accumulation of incompletely degraded oligosaccharides in cells and tissues and the corresponding increase of related free oligosaccharides in the urine. Clinical features can include bone abnormalities, coarse facial features, corneal cloudiness, organomegaly, muscle weakness, hypotonia, developmental delay, and ataxia. Age of onset ranges from early infancy to adult and can even present prenatally.

 

The sphingolipidoses are a subset of lysosomal storage disorders caused by a defect in any one of the enzymes that degrade complex ceramide containing lipids. They are characterized by the excessive accumulation of sphingolipids in the tissues, particularly in the central nervous system resulting in progressive neurodegeneration and developmental regression. In 2 conditions, Fabry disease and Gaucher disease type I, there is only systemic involvement. In many cases, sphingolipidoses can be detected by through oligosaccharide analysis in urine.

 

Because of the similarity of features across disorders and their variability, clinical diagnosis of LSDs can be challenging; therefore, urine screening and the combined analysis of multiple urine screening tests is an important tool for the initial workup of an individual suspected of having a lysosomal storage disorder. Abnormal results can be followed up with the appropriate enzyme or molecular analysis.

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.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

Abnormal results are not sufficient to conclusively establish a diagnosis of a particular disease. Follow-up testing is recommended to confirm a diagnosis.

 

When abnormal results are detected with characteristic patterns, a detailed interpretation is given, including an overview of the results and their significance, a correlation to available clinical information, elements of differential diagnosis, recommendations for additional biochemical testing, and in vitro confirmatory studies (enzyme assay and molecular test).

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Specific enzymatic or molecular assays should be used to confirm positive results.

 

In rare instances, a normal excretion of ceramide trihexosides may be seen in individuals who are carriers of, or affected with, Fabry disease. If Fabry disease is clinically suspected, see Fabry Disease Testing Algorithm in Special Instructions for additional testing recommendations.

 

Occasionally, an abnormal value for total glycosaminoglycans (GAG) will be obtained on a specimen that yields a normal liquid chromatography-tandem mass spectrometry (LC-MS/MS) pattern. This situation can occur as an artifact when a patient is treated with low-molecular-weight heparin. Other known causes are sample contamination with acrylic polymers used in disposable diapers and several clinical situations associated with excessive connective tissue destruction, bladder disease, or bone disease.

 

Not all lysosomal storage disorders are detectable through urine screening.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Scriver's The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). Part 16 Lysosomal Disorders. Accessed February 25, 2016. Available at http://ommbid.mhmedical.com/book.aspx?bookid=971

2. Enns GM, Steiner RD, Cowan TM: Lysosomal disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth. McGraw Hill Medical, 2009

3. Kingma SDA, Bodamer OA, Wijburg FA: Epidemiology and diagnosis of lysosomal storage disorders; challenges of screening. In Best Practice and Research Clinical Endocrinology and Metabolism. Volume 29, Issue 2, March 2015, pp 145-157, Available at www.sciencedirect.com/science/article/pii/S1521690X14000955

Special Instructions Library of PDFs including pertinent information and forms related to the test