ORNITHINE TRANSCARBAMYLASE (OTC DEFICIENCY)
OTC Sequencing
MITOCHONDRIAL DNA ANALYSIS

Description:
Ornithine transcarbamylase (OTC) deficiency is the most common of the urea cycle disorders. The hepatic urea cycle is the major route for waste nitrogen disposal. The enzyme catalyzes the condensation of carbamyl phosphate and ornithine to form citrulline, an essential step in the urea cycle. Mutations in the OTC gene cause enzyme deficiency, resulting in hyperammonemia. The gene is on the X-chromosome and is normally expressed in the mitochondrial matrix of the liver. Most of the affected are male, although female carriers may be symptomatic due to skewed X-inactivation. Affected children usually present soon after birth with symptoms including lethargy, vomiting, heavy or rapid breathing, poor feeding, seizures, irritability, decreased muscle tone, and disorientation. Mildly affected individuals and manifesting carriers may experience headaches with protein consumption avoid protein. Acute onset of symptoms may occur when metabolically stressed. The late-onset–affected male usually presents with no prior history consistent with hyperammonemia in childhood and suffers a rapid decompensation and demise, similar to the neonatal pattern. The OTC gene is approximately 73 kb in length, containing 10 exons. More than 100 different mutations have been described.

Reasons for Referral:

  • Confirmation of a clinical diagnosis
  • Carrier testing

Testing Methodology:
A PCR-based assay is used to amplify all exons and the immediately adjacent intronic regions of the OTC gene. Direct sequence analysis of PCR products is performed in both the forward and reverse directions using automated fluorescent dideoxy sequencing methods.

Specimen Requirements:
Blood:
EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc

Turnaround Time:
Index: 4 weeks
Known Familial Mutation:
2 weeks

CPT Codes and Prices:
Index: 83904x20, 83898x10, 83912, 83891, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

Shipping Information

Forms:
 >> Gene Sequencing Requisition or Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included
 >> Prenatal Requisition

References:
1. Tuchman M et al. (2002) Mutations and polymorphisms in the human ornithine transcarbamylase gene. Hum. Mutat. 19: 93-107.
2. The Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff.

Test Codes:
Index: 3140
Known Familial Mutation: 3141
Prenatal: 3142

Last Modified: 2-27-08