Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

1A2
89401
Urine Amino Acid
Reference Values (nmol/mg
creatinine)
Age Groups
< or =12
Months
13-35 Months 3-6 Years 7-8 Years 9-17 Years > or =18 Years
(n=36) (n=45) (n=39) (n=10) (n=40) (n=145)
Arginine Arg 10-560 20-395 14-240
Ornithine Orn
Cystine Cys 12-504 11-133 10-98
Lysine Lys 19-1988 25-743 14-307 17-276 10-240 15-271
Clinical References: 1. Knoll T, Zollner A, Wendt-Nordahl G, et al: Cystinuria in childhood and
adolescence: recommendations for diagnosis, treatment, and follow-up. Pediatr Nephrol 2005
Jan;20(1):19-24 2. Cystinuria. In The Metabolic and Molecular Bases of Inherited Disease. Eighth edition.
Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, 2001, pp
4909-4932
Cytochrome P450 1A2 Genotype
Clinical Information: Primary metabolism of many drugs is performed by cytochrome P450
(CYP), a group of oxidative/dealkylating enzymes localized in the microsomes of many tissues
including the intestines and liver. One of these CYP enzymes, CYP1A2, is wholly or partially
responsible for the hydroxylation or dealkylation of many commonly prescribed drugs (see above). The
current clinical application of this test is focused on the impact of allelic variation on antidepressant and
antipsychotic metabolism. CYP1A2-mediated drug metabolism is highly variable. CYP1A2*1A is the
wildtype or normal allele. Some individuals have altered CYP1A2 gene sequences that result in
synthesis defective enzyme. These individuals metabolize CYP1A2 substrates poorly. Changes in the
promoter impacting gene induction of the CYP1A2 gene has been observed, which results in either an
increase or decrease of overall metabolic activity. Dosing of drugs that are metabolized through
CYP1A2 may require adjustment based on the individual patient's genotype. Patients who are poor
metabolizers may require lower than usual doses to achieve optimal response. Patients who are
ultrarapid metabolizers may benefit from increased doses. Patients with either ultrarapid or poor
metabolism also may benefit by conversion to other comparable drugs that are not primarily
metabolized by CYP1A2. A number of specific polymorphisms have been found in the CYP1A2 gene
that results in enzymatic deficiencies. The frequency of these polymorphisms varies within the major
ethnic groups. All of the identified polymorphisms associated with CYP1A2 are autosomal recessive.
Consequently, only individuals who are homozygous or compound heterozygous for these
polymorphisms are poor metabolizers. Individuals who are heterozygous, with 1 normal gene and 1
defective polymorphic gene, will have metabolism intermediate between the extensive (normal) and
poor metabolizers. The following information outlines the relationship between the polymorphisms
detected in this assay and the effect on the activity of the enzyme produced by that allele: Nucleotide
Change Effect on Enzyme Metabolism* -3860G->A Lower inducibility in Asians but increased
inducibility in Northern Europeans -2467T->del T Increased inducibility -729C->T Decreased activity
and decreased inducibility -163C->A Increased inducibility 125C->G Greatly reduced activity 558C->A
Greatly reduced activity 2385G->A Decreased activity 2473G->A Greatly reduced activity 2499A->T
Decreased activity 3497G->A Decreased activity 3533G->A No activity 5090C->T Greatly reduced
activity 5166G->A Decreased activity *Effect of a specific polymorphism on the activity of the
CYP1A2 enzyme can only be estimated since the literature does not provide precise data. A
complicating factor in correlating CYP1A2 genotype with phenotype is that some drugs or their
metabolites are inhibitors of CYP1A2 catalytic activity. These drugs may reduce CYP1A2 catalytic
activity. Consequently, an individual may require a dosing decrease greater than predicted based upon
genotype alone. Another complicating factor is that the CYP1A2 gene is inducible by several drugs and
environmental agents (eg, cigarette smoke) and the degree of inducibility is under genetic control. It is
important to interpret the results of testing in the context of other coadministered drugs and
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