Mucopolysaccharides in urine

Recently Heremans demonstrated mucopolysaccharides in urine after zone electrophoresis by means of an Alcian blue-acid fuchsin staining technique (HI).3 Applied in our laboratory to a curtain after a run of serum, two fractions, references -)- 86.30 and - - 86.12, were demonstrated but do not seem to be regular components of serum, at least not in that high concentration (Fig. 62c). 

The urine of patients with gargoylism, of both the autosomal recessive and sex-linked types, contains abnormally high amounts of acid mucopolysaccharides. Determination (T2) of the acid mucopolysaccharides in urine in relationship to preformed creatinine is useful in distinguishing certain cases of gargoylism from other conditions with which they are sometimes clinically confused (e.g., cretinism and chondro-osteo-dystrophies of the Morquio-Brailsford type). Another simple diagnostic test for gargoylism is based on the presence in the lymphocytes of abnormal inclusions of acid mucopolysaccharides which are revealed by staining (M24). 

B4. Berenson, G. S., and Serra, M. T., Mucopolysaccharides in urine from patients with Marfan s syndrome. Federation Proc. 18, 190 (1959). 

D33. Douglas, C., Nowak, J., and Danes, B. S., Mucopolysaccharides in urine during normal human development. Pediat. Res. 7, 724-7ZT (1973). 

W7. Wessler, E., Determination of acidic glycosaminoglycans (mucopolysaccharides) in urine by an ion exchange method. Application to coUagenoses , gargoylism, the nail-patella syndrome and Farber s disease. Clin. Chim. Acta 16,235-243 (1967). 

While esters of sulfuric acid do not play as central a role in metabolism as do phosphate esters, they occur widely. Both oxygen esters (R-0-S03 , often referred to as O-sulfates) and derivatives of sulfamic acid (R-NH-SOg, N-suIfates) are found, the latter occurring in mucopolysaccharides such as heparin. Sulfate esters of mucopolysaccharides and of steroids are ubiquitous and sulfation is the most abundant known modification of tyrosine side chains. Choline sulfate and ascorbic acid 2-sulfate are also found in cells. Sulfate esters of phenols and many other organic sulfates are present in urine. 

The concentration of acid mucopolysaccharides in serum, and their excretion in urine, are increased in patients with rheumatoid arthritis (D7), lupus erythematosus (D6), diabetes (C7), and leukemia (R2, SIO) and other malignant diseases (R2). The daily urinary excretion of acid mucopolysaccharides was within the normal range in cases of acute hepatitis, but was usually increased in chronic hepatitis and in florid cirrhosis (K5). A decrease in the amount of acid mucopolysaccharides excreted was found in primary hepatoma, whereas in most cases of obstructive jaundice the amount was markedly increased (K5). 

M21. Meyer, K., Hoffman, P., Linker, A., Crumbach, M. M., and Sampson, F., Sulfated mucopolysaccharides of urine and organs in gargoylism (Hurler s syndrome) II. Additional studies. Proc. Soc. Exptl. Biol. Med. 102, 587-590 (1959). 

The measurement of urinary uronic acid has been used as an early indicator in the development of renal papillary necrosis in rats given multiple doses of N-phenylanthranilic acid or mefenamic acid [217]. A significant elevation of uronic acid in urine occurred was well ahead of the development of histological evidence of renal papillary necrosis. The biochemical basis of these changes appears to be related to acid mucopolysaccharides accumulation [218]. 

K7. Kerby, G. P., The excretion of glucuronic acid and of mucopolysaccharides in normal human urine. J. Clin. Invest. 33, 1168 (1954). 

B31. Bitter, T., Siegenthaler, P., DePreux, T., and Martin, E., Excretion in the urine of aminoacridine precipitable polyuronides (acid mucopolysaccharides) in patients with rheumatoid arthritis. Ann. Rheum. Dis. 29, 427-433 (1970). 

Uric acid bears a very close relation to urinary stones. Uric acid stones appear very often in patients with a high uric acid blood concentration and increased uric acid excretion in the urine. But an increase of uric acid in urine can also promote the formation of calcium oxalate stones because uric acid blocks the inhibitory activity of the acid mucopolysaccharides on the precipitation of calcium oxalate (6). 

A substance with similar immunological properties has been found in the kidney, where it is more abundant in the cortex than in the medulla. According to Boyce and King [90, 91], the mucoprotein is consistently found in the kidneys of patients with recently formed stones, but is rarely present in patients with other kidney diseases in which stones are not formed (e.g., renal carcinoma and severe renal arteriosclerosis). The mucoprotein has not been detected in normal kidneys or in patients with pyelonephritis, and the compound cannot be immunologically detected in blood serum, human saliva, or bone matrix. The only other tissue where this matrix substance has been detected is the intestine. (Boyce and King think that this is not a coincidence and that the reason for its presence in kidney and intestine is that both these organs are involved in calcium absorption.) But most important to the pathogenesis of lithiasis are the mucopolysaccharides found in urine. 

Type Mucopolysaccharidosis Name Genetics Clinical features Mucopolysaccharides in the urine... 

Laboratory findings are characterized by increased urinary excretion of mucopolysaccharides (Dorfman and Lorincz 1957), with values of 60 mg per liter and more as compared to normal values of 5—10 mg per liter. The urinary mucopolysaccharides in HD consist of chondroitinsulfate B and heparitin sulfate (Dorfman and Lorincz 1957, Meyer et al. 1958) with a 2 1 ratio. The occurrence of both mucopolysaccharides is used for distinction of HD from other mucopolysaccharidoses or other disorders associated with increased mucopolysaccharide excretion, such as the Marfan syndrome (Berenson and Dalferes 1965). The finding of a smaller proportion of heparitinsulfate in HD as compared to the sex-linked mucopolysaccharidosis II (see table 8) (Terry and Linker 1964) is not obligatory. Increased arylsulfatase B activity was found in the urine of patients with HD by Austin et al. (1964). 

The mucopolysaccharidoses can be diagnosed by the detection and identification of the excess mucopolysaccharides in the urine. 

Compounds known to behave in this way in vivo are listed in recent reviews in this Series.1 2 The structures of some of the /3-D-glucopyranosiduronic acids isolated from urine have been proved by chemical synthesis.3 A few similar derivatives of flavones and triterpenes have been isolated from plants. D-Glucuronic acid also occurs in mammalian tissues as a constituent of acid mucopolysaccharides (aminodeoxypolysaccharides, containing uronic acid), such as hyaluronic acid, chondroitinsulfate, and heparin,4 and it is a direct precursor of L-ascorbic acid in plants and mammals.6 It is present in many of the plant polysaccharides classified as hemicelluloses6 and gums,7 and it has also been found in certain bacterial polysaccharides.4... 

The metabolic disorder in Morquio-Ullrich s disease differs from that in Hurler s syndrome since substantial quantities of keratan sulfate have been identified (P2) in the urine of patients with this disease. The identification of the mucopolysaccharide was based on chemical, chromatographic, and infrared spectral data. In view of this rigorous characterization, it seems likely that the glucosamine-containing mucopolysaccharide reported by other workers (M6) in the urine of cases of this disease is also keratan sulfate. 

The amounts of acid mucopolysaccharides excreted in the urine of two families with this disease were comparable to those excreted in... 

Smail crystals of calcium oxalate are a normal component of the urine. They form in the glomerular filtrate as water is reabsorbed and the urine is concentrated, Theurineofmostpersonscontainscompoundsthat inhibit the grow th of c rysta Is. These inhibitors include magnesium, citrate, pyrophosphate, and mucopolysaccharides. Apparently, persons who tend to form renal and bladder stones have reduced levels of these Inhibitors. Slone formation has a genetic component. The disease may "run in the family."... 

D34. Duncan, D. M., Logan, R. W., Ferguson-Smith, M. A., and Hall, F., The measurement of acid mucopolysaccharides (glycosaminoglycans) in amniotic fluid and urine. Clin. Chitn. Acta 45, 73-83 (1973). 

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