Assuming that the popular ans is correct, here is a self assessment question on the topic A 2-month-old boy is admitted to the hospital for failure to thrive. You note him to have fatty stools, and consider cystic fibrosis in your differential diagnosis. You order pilocarpine iontophoresis, but the laboratory calls to say they could not collect enough sweat from the infant. Which of the followingis another way to make the diagnosis of cystic fibrosis? A. Quantitative fecal fat B. Bronchoscopy and bronchoalveolar lavage C. Pilocarpine iontophoresis for both parents D. DNA testing for cystic fibrosis transmembrane regulator (CFTR) mutations E. Pancreatic biopsy EXPLANATION: Cystic fibrosis (CF) has an autosomal recessive pattern of inheritance; both parents are usually heterozygous, and the affected child may be a homozygote (two copies of the same mutation) or a compound heterozygote (one copy of each of two different mutations). The F508 mutation, present in about 70% of North American whites, is the most common. In Europe, the incidence of this mutation ranges from 40% to 80% in different population groups. Many other mutations vary in specific ethnic groups. Identification of a CF mutation in both chromosomes, whether homozygous or compound heterozygous, would be diagnostic in 72%. DNA testing can help predict manifestations of the disease, especially pancreatic involvement. Pancreatic insufficiency is present in 99% of patients who are homozygous for F508, in 72% who are compound homozygous for F508, and in only 32% who do not carry the F508 mutation. DNA analysis for carrier testing is now recommended for relatives of CF patients and for reproductive partners of carriers. Its role in mass population screening is controversial. The sweat test is diagnostic in virtually all cases of classic CF and is equally useful in all ethnic groups, but it is not useful in detecting heterozygotes. DNA testing is of value for postmortem investigations as well as in sick premature infants and other patients for whom sweat collection is unsuccessful. While genetic testing does not include all of the estimated 1500 defects in the CFTR, it does include 30 to 80 of the most common mutations, representing more than 90% of affected individuals with two CFTR mutations. Sweat testing of asymptomatic parents would not be helpful. While the other studies may indeed be abnormal in a patient with cystic fibrosis, they are not diagnostic. The answer is D.
