OTC Sequence Analysis

Clinical Use

Use

The OTC Sequencing Analysis is conducted to identify pathogenic variants in the OTC gene associated with ornithine transcarbamylase deficiency, a genetic disorder that affects the urea cycle. The condition is severe and typically manifests within days after birth, primarily in males, leading to neurological damage due to toxic ammonia buildup in the bloodstream. Symptoms can escalate quickly, with neonates presenting with muscle weakness, seizures, and hypothermia, while older individuals may experience episodic vomiting and developmental delays. Early diagnosis and management of ammonia levels are vital, and a liver transplant is often necessary for affected infants. Genetic testing is crucial to establish a diagnosis, particularly for symptomatic individuals or those with a family history of the condition, ensuring timely treatment and intervention.

Special Instructions

If testing for a variant previously identified in an affected family member, please order test code 3141. Testing is indicated for patients with clinical diagnosis or family history of OTC deficiency, including those with positive newborn screening results or those planning a pregnancy. Blood must be drawn in EDTA tubes or saliva collected using the Oragene DNA Self-Collection Kit provided by MGL. Shipping conditions stress the importance of avoiding heat or freezing during transport.

Limitations

While the test is effective in identifying the majority of pathogenic variants in the OTC gene, there are limitations regarding the detection of intronic variants and large rearrangements. Some mutations that do not affect the coding sequence may be missed. Moreover, genetic heterogeneity in OTC deficiency can lead to variants not being identifiable through standard sequencing methods, necessitating comprehensive family history assessment and sometimes additional testing strategies to ensure a complete understanding of a patient's genetic status regarding OTC deficiency.

Test Details