Urine tests are a non-invasive, cost-effective tool that can diagnose Ehlers-Danlos syndrome or EDS, a group of connective tissue disorders. EDS is caused by mutations in the genes encoding for different collagen proteins or collagen-associated proteins.
These mutations lead to characteristic EDS symptoms that include hypermobility in the joints and skin hyperextensibility.
What are urine tests?
Urinalysis, or urine tests, can be used to diagnose some types of EDS. The tests detect changes in the concentration of a specific chemical compound that can directly indicate the underlying disease. They also can be used to monitor disease progression and the efficacy of treatments.
How do urine tests work?
Produced in the body by the kidneys, urine filters out waste from the blood. This helps regulate the water and electrolyte levels in the body. Changes in the color and chemical composition of urine can be used to detect disease.
During urinalysis, the following are checked:
- changes in the color, clarity, and acidity (pH) of urine
- changes in the chemical composition of urine, and the presence of sugar, protein, fat, and other molecules
- presence of different types of cells, including blood cells
Urine tests and EDS
Urine test for kyphoscoliotic and spondylodysplastic EDS
Deoxypyridinoline (LP) and pyridinoline (HP) are compounds that are formed when two lysine or hydroxylated lysine amino acids of adjacent collagen protein molecules are cross-linked. Amino-acids are building blocks of proteins. These compounds are found in urine because of the natural turnover of collagen. Their amount in urine can be measured in the laboratory using a technique called high‐performance liquid chromatography (HPLC).
In kyphoscoliotic EDS (kEDS), there is a deficiency in the lysyl hydroxylase 1 enzyme. That enzyme hydroxylates, or adds a hydroxyl (OH) group to the lysine amino acid in collagen. As a result, LP levels are significantly higher than those of HP in the urine of people with kEDS. Urine tests that show an LP/HP ratio between 2 and 9 indicate kEDS. The normal LP/HP ratio in urine is 0.2.
Changes in the LP/HP ratio also are seen in the urine of people with spondylodysplastic EDS (spEDS), which is caused by mutations in the SLC39A13 gene. This gene encodes for a protein called ZIP13 that transports zinc ions into the cells. Zinc is essential for the enzymes that hydroxylate lysine. So, the mutation contributes to abnormal LP/HP ratio. The LP/HP ratio in the urine of people with spEDS is about 1.0.
Urine test for musculocontractural EDS
In musculocontractural EDS (mcEDS), there is a defect in a complex sugar molecule called dermatan sulfate. Dermatan sulfate usually is found cross-linked in the connective tissues with another complex sugar called chondroitin sulfate. Thus, the normal metabolic breakdown of the connective tissue generates chains of chondroitin sulfate/dermatan sulfate. The amounts of these chains can be measured in urine using a technique called anion chromatography. In patients with mcEDS, defective dermatan sulfate cannot bind to chondroitin sulfate and therefore is not present in urine.
Last updated: Nov. 7, 2019
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