A newborn was delivered two days ago at home without any complications. Today, he was brought in for examination. The baby has a fever and a distended abdomen that's rigid on palpation. The mother mentions her son started vomiting a green fluid and that he has yet to pass his first stool. She also says she didn’t have access to prenatal care throughout the pregnancy. An x-ray was performed, and it showed air-fluid levels and dilated bowel loops, along with a “soap bubble” appearance. A pilocarpine-induced sweat test was done which showed a Cl- level over 60.
Now, the newborn seems to have cystic fibrosis. But first, a little physiology. Normally, elements like ions and water come in and out of the cell through specific channels located on the cell’s membrane. A very high yield fact you need to know is that there’s this particular channel called “cystic fibrosis transmembrane conductance regulator” or the CFTR protein, which is an ATP-gated channel, meaning it works by using ATP for energy. It transports negatively charged Cl-. In cells that produce mucus, it secretes the ion out of the cell, and in cells of the sweat glands, it reabsorbs Cl- back into the cell. Now, normally, cells in mucus membranes pump out chloride ions into the thick mucus, which helps attract water and make it less viscous. This mucus will protect the lining of organs and tissues like the airways, digestive system, and reproductive system. For example, the mucus produced by the glands in the airways allows the tiny cilia to sweep back and forth. This sweeping motion helps move the mucus and the bacteria or foreign particles trapped in it, out of the airways. Additionally, the CFTR protein also regulates the function of other channels, such as those that transport positively charged sodium ions.
Now, cystic fibrosis, or CF, is an autosomal recessive disorder where there’s a mutation in the CFTR gene, and it is considered to be the most common lethal genetic disease in the Caucasian population. Keep in mind that the defective gene is located on chromosome 7 and that the defect itself is usually represented by ∆F508, an abbreviation which indicates that there’s a deletion of three nucleotides that code for phenylalanine at amino acid position 508. Another thing to know is that the ∆F508 mutation results in impaired post-translational processing. This means that the protein will be misfolded and it will not be glycosylated, so it’ll be retained in the endoplasmic reticulum, where it is degraded instead of being released to the cell membrane.