Sorted By Test Name - Mayo Medical Laboratories

1A2
89401
Reference Values:
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
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