Cystinuria

H2N (CH2]5 NH2. a syrupy fuming liquid, b.p. 178-180 - C. Soluble in water and alcohol. Cadaverine is one of the ptomaines and is found, associated with pulrescine, in putrefying tissues, being formed by bacterial action from the amino-acid lysine. It is found in the urine in some cases of the congenital disease cystinuria. The free base is poisonous, but its salts are not. 

Hyperargininemia. This defect is characterized by elevated blood and cerebrospinal fluid arginine levels, low erythrocyte levels of arginase (reaction 5, Figure 29-9), and a urinary amino acid pattern resembling that of lysine-cystinuria. This pattern may reflect competition by arginine with lysine and cystine for reabsorption in the renal tubule. A low-protein diet lowers plasma ammonia levels and abolishes lysine-cystinuria. 

There are numerous abnormalities of cysteine metabolism. Cystine, lysine, arginine, and ornithine are excreted in cystine-lysinuria (cystinuria), a defect in renal reabsorption. Apart from cystine calculi, cystinuria is benign. The mixed disulfide of L-cysteine and L-homocysteine (Figure 30-9) excreted by cystinuric patients is more soluble than cystine and reduces formation of cystine calculi. Several metabolic defects result in vitamin Bg-responsive or -unresponsive ho-mocystinurias. Defective carrier-mediated transport of cystine results in cystinosis (cystine storage disease) with deposition of cystine crystals in tissues and early mortality from acute renal failure. Despite... 

Pfeiffer, R., et al. Luminal hetero-dimeric amino acid transporter defective in cystinuria. Mol. Biol. Cell 1999, 10, 4135-4147. 

Feliubadalo, L., et al. Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT. International Cystinuria Consortium. Nat. Genet. 1999, 23, 52-57. 

Penicillamine has also been used in cystinuria and for the treatment of rheumatoid arthritis. Discovery of its chelating properties led to its use in patients with Wilson s disease (hepatolenticular degeneration) and heavy-metal intoxications. Penicillamine is administered by mouth and should be taken on an empty stomach [4],... 

Cystinuria. Penicillamine reduces excess cystine excretion in cystinuria. Penicillamine with conventional therapy decreases crystalluria and stone formation, and may decrease the size of or dissolving existing stones. This is achieved by disulfide interchange between penicillamine and cystine, resulting in a substance more soluble than cystine and readily excreted. 

If this is so, then the next question to be answered is What metabolic peculiarities are crucial with respect to susceptibility to alcoholism It is obvious that the answer to this question must be based upon some knowledge of metabolic peculiarities in general. What metabolic peculiarities exist from which one might choose the crucial ones Because of lack of attention to biochemical individuality, little indeed was known about metabolic peculiarities. When we began the study of alcoholism, the list of known peculiarities was pretty much limited to the relatively rare so-called "inborn errors of metabolism," alcaptonuria, phenyl ketonuria, cystinuria, and the like. The chance that any of these were involved was very minute. 

Not indicated for the following Not indicated for cystinuria rheumatoid arthritis biliary cirrhosis. 

Lupus erythematosus Certain patients will develop a positive antinuclear antibody (ANA) test and some may show a lupus erythematosus-like syndrome similar to other drug-induced lupus, but it is not associated with hypocomplementemia and may be present without nephropathy. A positive ANA test does not mandate drug discontinuance however, a lupus erythematosus-like syndrome may develop later. Sensitivity reactions Once instituted for Wilson s disease or cystinuria, continue treatment with penicillamine on a daily basis. Interruptions for even a few days have been followed by sensitivity reactions after reinstitution of therapy. 

Dietary suppiementation Because of their dietary restriction, give patients with Wilson s disease, cystinuria, and rheumatoid arthritis whose nutrition is impaired 25 mg/day of pyridoxine during therapy, because penicillamine increases the requirement for this vitamin. 

Cystinuria, also called cystine urolithiasis, arises from impaired reabsorptive transport of cystine... 

Symptoms of cystinuria, which develop during the teenage years to early adulthood, are those typically caused by recurring kidney stones, such as pain in the side or back often of a severe or debilitating nature. 

Cystinuria is an autosomal recessive disease with an incidence of 1 In 15,000 live births in the United States. 

The answer is D. The patient s symptoms are consistent with a kidney stone, which is confirmed by the radiographic finding. The etiology of the stone is indicated by the urinalysis data, which suggest cystinuria. The cells of this patient s renal proximal tubules would be deficient in a transporter responsible for the reabsorptive uptake of cystine and the basic amino acids, arginine, lysine, and ornithine. Failure of the tubules to reabsorb these amino acids from the ultrafiltrate causes them to be excreted at high concentration in the urine. 

Wilson s disease PO Initially, 250 mg4 times/day (some pts may begin at 250 mg/day gradually increase). Dosages of 750-1,500 mg/day that produce initial 24-hr cuprure-sis >2 mg should be continued for 3 mo. Maintenance Based on serum-free copper concentration (<10 mcg/dl indicative of adequate maintenance). Maximum 2 g/day. Cystinuria PO Initially, 250 mg/day Gradually increase dose. Maintenance 2 g/day. Range 1-4 g/day... 

Patients with cystinuria should drink large amounts of water... 

Inborn errors of metabolism (Eanconi s syndrome, cystinuria)... 

It is used in poisoning due to copper, mercury and lead Wilson s disease, cystinuria, scleroderma and rheumatoid arthritis. 

The cyanide nitroprusside test determines the presence of free sulfhydryl or disulfide compounds in urine samples [1, 3,4]. During the first step of the assay, cyanide reduces any disulfides that are present to free sulfhydryl compounds. In the second step, a reddish color reaction results when the free sulfhydryl groups complex with nitroprusside. A positive result is most usually due to cystine in the urine. Familial cystinuria is among the most common aminoacidurias. Disulfides are also excreted in other metabolic disorders such as homo cystinuria and ji-m e reap lol ac la le - cy s lei ne disulfiduria. Both will also produce positive results according to the following reaction RSH + Na2Fe(CN)5NO (sodium nitroprusside) — chromophore + NO. 

Cystathionine, methionine, and taurine are not detected by this assay. In addition, this assay may be helpful for the detection of heterozygotes of cystinuria types 2 and 3. 

Inherited defects of amino acid catabolism, biosynthesis, or transport have been known for many years the number of novel defects is only slowly increasing [1,3,4, 10, 12]. In this respect, cystinuria was among the first four inherited metabolic diseases described by Garrod 100 years ago. The disease with the highest impact on the community - phenylketonuria (PKU) - was discovered as early as the 1930s. Despite its early discovery, PKU remains a mysterious disease in several aspects, and patient-oriented research of this condition continues today. 

Fig. 2.1.2a-c A Urine amino acids in a patient with cystinuria assayed by an amino acid analyzer (AAA). The indicated peaks are 1 glycine, 2 cystine, 3 ammonia, 4 ornithine, 5 lysine, 6 arginine, i.s. internal standard (S-amino thyl-cysteine). Cystinuria treatment is best followed-up by analyzing an early morning urine specimen, which usually shows the highest amino acid concentrations. b-c see next page... 

Cystinuria is a disorder of the proximal tubule s reabsorption of filtered cystine and dibasic amino acids (lysine, ornithine, arginine). 

Incidence of inherited diseases of amino acid metabolism. [Note Cystinuria is the most common genetic error of amino acid transport.]... 

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