Review Question - QID 108475

This case is most consistent with a diagnosis of cystic fibrosis, which is most commonly caused by a phenylalanine deletion at position 508 of the CFTR gene on chromosome 7.

Chronic infections in childhood are generally caused by an inherited defect in the body's defense mechanisms. These mutations can either affect immune system cells or the physical mechanisms protecting exposed membrane surfaces. Determining the cause often requires identification of specific organisms or associated symptoms. In this case, the patient suffers from chronic lung infections that are most likely caused by Pseudomonas aeruginosa given the production of the characteristic blue/green pigment pyocyanin. This infection is closely associated with cystic fibrosis although it can also be found as part of more generalized infections in asplenic patients or patients with B cell deficiencies. The diagnosis of cystic fibrosis is supported by the physical exam findings of nasal polyps and pancreatic insufficiency (as seen by the fatty diarrhea due to malabsorption). It is caused by autosomal recessive inheritance of a deleterious mutation in the chloride channel CFTR. This leads to excessive reabsorption of salt and water from excretions, leading to a thick obstructive mucus in the lungs and pancreatic ducts. The CFTR gene is located on chromosome 7.

Incorrect Answers:
Answer 2: Chromosome 11 contains the hemoglobin gene and can be responsible for a number of hemoglobinopathies such as sickle cell disease and thalassemia. These diseases can lead to infections with pseudomonas due to functional asplenia (pseudomonas is an encapsulated organism, and the spleen is key to removing these organisms); however, the associated symptoms of pancreatic insufficiency and nasal polyps would not be seen in these diseases.

Answer 3: Chromosome 17 is the location of the neurofibromatosis type 1 gene. Neurofibromatosis and other neurocutaneous diseases may manifest with polyps or other growths but do not classically lead to abnormal infections as seen in this case.

Answer 4: Chromosome 22 contains the chromosome region responsible for DiGeorge syndrome, which can present with symptoms of immunodeficiency due to thymic hypoplasia; however, the associated findings of DiGeorge syndrome are hypoparathyroidism and cardiac defects, rather than pancreatic insufficiency.

Answer 5: The X chromosome contains many genes responsible for X-linked disorders, including several immunodeficiency syndromes (most notably Bruton's agammaglobulinemia). These syndromes usually lead to generalized infections of large classes of organisms.

Bullet Summary:
Recurrent lung infections, especially with pseudomonas, in the setting of nasal polyps and pancreatic insufficiency are almost always associated with cystic fibrosis. This disease is caused by an autosomal recessive deficiency in the chloride channel CFTR.