Diagnosis of cystinuria
Biochemical diagnosis of cystinuria. Measures cystine, lysine, ornithine, and arginine.
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Amino Acid
Cystine, Quantitative, Urine (order when client indicates 24 hr TV)
Cystinuria
Urine
Question ID | Description | Answers |
---|---|---|
TM38 | Collection Duration | |
VL36 | Urine Volume |
Supplies: Urine Tubes, 10 mL (T068)
Specimen Volume: 5 mL
Collection Instructions:
1. Collect before intravenous pyelogram.
2. Collect urine for 24 hours.
3. Add 20 mL of toluene as preservative at start of collection. If toluene is not available, refrigerate during collection.
4. Mix well before taking 5-mL aliquot.
Additional Information: See Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens in Special Instructions for multiple collections.
If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Note: The addition of preservative or application of temperature controls must occur within 4 hours of completion of the collection.
| No |
Refrigerate | OK |
Frozen | OK |
50% Acetic Acid | No |
Boric Acid | No |
Diazolidinyl Urea | No |
6M Hydrochloric Acid | No |
6M Nitric Acid | No |
Sodium Carbonate | No |
Thymol | No |
Toluene | Preferred |
1 mL
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability. |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Urine | Frozen (preferred) | 70 days | |
Refrigerated | 14 days |
Diagnosis of cystinuria
Biochemical diagnosis of cystinuria. Measures cystine, lysine, ornithine, and arginine.
Cystinuria is an inborn error of metabolism resulting from poor absorption and reabsorption of the amino acid cystine in the intestines and kidneys. This leads to an accumulation of poorly soluble cystine in the urine and results in the production of kidney stones (urolithiasis). Symptoms may include acute episodes of abdominal or lower back pain, presence of blood in the urine (hematuria), and recurrent episodes of kidney stones may result in frequent urinary tract infections, which may ultimately result in renal insufficiency. The combined incidence of cystinuria has been estimated to be 1 in 7000.
Cystinuria is an autosomal recessive disease, but some heterozygous carriers have an autosomal dominant, incomplete penetrance appearance with elevated, but typically nondisease causing, urinary cystine excretion. Cystinuria is caused by variants in genes, SLC3A1 on chromosome 2p and SLC7A9 on chromosome 19q. Initially, the disease was classified into subtypes I, II, and III (type II and III are also referred as nontype-I) based on the amount of urinary cystine excreted in heterozygous parental specimens. A new classification system has been proposed to distinguish the various forms of cystinuria: type A, due to variants in the SLC3A1 gene; type B, due to variants in the SLC7A9 gene; and type AB, due to 1 variant in each SLC3A1 and SLC7A9 gene.
CYSTINE
3-15 years: 11-53 mcmol/24 hours
> or =16 years: 28-115 mcmol/24 hours
LYSINE
3-15 years: 19-140 mcmol/24 hours
> or =16 years: 32-290 mcmol/24 hours
ORNITHINE
3-15 years: 3-16 mcmol/24 hours
> or =16 years: 5-70 mcmol/24 hours
ARGININE
3-15 years: 10-25 mcmol/24 hours
> or =16 years: 13-64 mcmol/24 hours
Conversion Formulas:
Result in mcmol/24 hours x 0.24=result in mg/24 hours
Result in mg/24 hours x 4.17=result in mcmol/24 hours
Homozygotes or compound heterozygotes with cystinuria excrete large amounts of cystine in urine, but the amount varies markedly. Urinary excretion of other dibasic amino acids (arginine, lysine, and ornithine) is also typically elevated. Plasma concentrations are generally normal or slightly decreased.
Individuals who are homozygous and heterozygous for nontype I cystinuria can be distinguished by the pattern of urinary amino acids excretion: homozygous individuals secrete large amounts of cystine and all 3 dibasic amino acids, whereas heterozygous individuals secrete more lysine and cystine than arginine and ornithine.
No significant cautionary statements
1. Saravakos P, Kokkinou V, Giannatos E: Cystinuria: current diagnosis and management. Urology. 2014 Apr;83(4):693-699
2. Palacin, M, Goodyer, P, Nunes V, Gasparini P: Cystinuria. Palacin M, Goodyer P, Nunes V, Gasparini P: Cystinuria. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed April 27, 2022. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225555540&bookid=2709
Quantitative analysis of the amino acids (AA) cystine, lysine, arginine, and ornithine is performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) by labeling amino acids present in urine with aTRAQ Reagent 121. Samples are dried and reconstituted with aTRAQ Reagent 113-labeled Standard Mix. Amino acids are separated and detected by LC-MS/MS. The concentrations of amino acids are established by comparison of their ion intensity (121-labeled amino acids) to that of their respective internal standards (113-labeled amino acids). Chromatography is performed using a C18 (150x4.6mm) column and total analysis time is 18 minutes.(Unpublished Mayo method)
Monday through Friday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
82136
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
CYSQN | Cystinuria Profile, QN, 24 hour | 90785-7 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
TM38 | Collection Duration | 13362-9 |
VL36 | Urine Volume | 3167-4 |
3583 | Cystine | 13966-7 |
3589 | Lysine | 25464-9 |
3590 | Ornithine | 25491-2 |
3591 | Arginine | 25322-9 |
50447 | Reviewed By | 18771-6 |