Carbamoyl phosphate synthetase I deficiency is an inherited disorder characterized by accumulation of ammonia in the blood. The most severe form occurs in the first 24-72 hours following birth, after feeding begins and milk proteins start to be broken down in the liver. If left untreated, affected neonates often die due to severe metabolic derangements; survivors often develop permanent neurologic injury. The estimated incidence of carbamoyl phosphate synthetase I deficiency is about 1 in 800,000 newborns. If a decision is made to test all newborns for this disease, then this initial test should be designed to have a high:

Question

Carbamoyl phosphate synthetase I deficiency is an inherited disorder characterized by accumulation of ammonia in the blood.  The most severe form occurs in the first 24-72 hours following birth, after feeding begins and milk proteins start to be broken down in the liver.  If left untreated, affected neonates often die due to severe metabolic derangements; survivors often develop permanent neurologic injury.  The estimated incidence of carbamoyl phosphate synthetase I deficiency is about 1 in 800,000 newborns.  If a decision is made to test all newborns for this disease, then this initial test should be designed to have a high:

Quizplus · Accepted Answer

Carbamoyl phosphate synthetase I deficiency is a rare disorder (incidence 1 in 800,000 newborns) with serious and possible irreversible consequences if not detected and treated early. Therefore, it is important to identify all individuals who potentially have the disease using a screening test that can be performed on a large number of newborns. Although an ideal screening test would be highly sensitive and specific, developing a test that has both of these properties is often not possible, and so a compromise must be made. The sensitivity of a test refers to its ability to correctly identify those with the disease: it is the probability of the test returning a positive result in a person with the disease. A highly sensitive test will ensure that most patients with the disease will have a positive test result (leading to few false negative results); therefore, fewer cases of disease are missed. Given a test with high sensitivity, a negative result would help to rule out a diagnosis (SnNout). This is important during screening for life-threatening diseases, even if obtaining a high sensitivity causes an increased numbers of false positives (ie, reduced specificity). (Choice A) Setting a high cutoff value typically (but not always) produces higher specificity and lower sensitivity. (Choices B and E) Specificity represents the ability of a test to correctly identify those without the disease. A very specific test has a low rate of false positives, so most healthy patients will have a negative test result (true negative). Given a test with high specificity, a positive result would help to rule in a diagnosis (SpPin). Confirmatory tests with high specificity are often used on patients who test positive on a screening test to ensure that a patient actually has the disease. (Choice C) Positive predictive value refers to the probability that a disease is present given a positive test result. Positive predictive value depends on disease prevalence. When screening patients for a rare disorder, positive predictive value will often be low due to a high number of false positives. Educational objective: The sensitivity of a test refers to its ability to correctly identify those with the disease. A highly sensitive test should always be considered over a highly specific test when screening for life-threatening diseases, where identification of every person with the disease is important.

Carbamoyl Phosphate Synthetase I Deficiency Is an Inherited Disorder Characterized