Cystic fibrosis is a progressive, disabling disease of mucus glands in the lungs, liver, pancreas, and the intestines. Thick, and teeming with microbes, the mucus produced is abnormal; in the shelter of matrices called biofilms, rank parches of infection bloom beyond the reach of immune defenses or antibiotics. Over time, glutinous secretions and chronic infection so damage the lungs that the bronchi are chronically inflamed; they dilate, collapse and obstruct the flow of air. Secretions collect in the small airways of the lungs. The normal structure of the lower airways is altered.
The disease is associated with replication gone wrong. Chromosome seven houses the genes peculiar to this disorder. Mutations are changes in the sequence of elements in the structure of the genes. They can be caused by copying errors in the genetic material during cell division or by external factors, and in turn give rise to discrepancies in a set of unique alleles in a population, the gene pool. At the locus q, three hundred twelve of chromosome seven, a mutated regulatory gene responsible for conducting fluids across membranes causes the expression of Cystic Fibrosis. The gene normally creates a chloride ion channel essential for making sweat, digestive juices, and mucus. Parents pass to their children combinations of genes or copies of genes (alleles). Cystic Fibrosis develops when none of these combinations can produce the normal regulatory protein. The most common mutation, the deletion at delta F five hundred eight results in a loss of the amino acid phenylalanine. It produces an abnormally folding protein that is of no use to the cell which breaks it down, and it accounts for seventy percent of Cystic Fibrosis worldwide and ninety percent of cases in the United States. Over fourteen hundred mutations produce the disease.
What are the problems the mutations cause at the cellular level? There are several. Some produce the protein too quickly and the end products are too short or they are broken down too fast; some cannot make use of energy or cross the chloride membrane. Others generate too few protein copies. The result of all of these errors is the disease process of Cystic Fibrosis. It can be diagnosed before birth by genetic testing or by screening tests carried out just after birth. The diagnosis may be confirmed by a sweat test. Cystic Fibrosis is an autosomalrecessive disease. It is common among the European and the Ashkenazi Jewish populations; one in twenty-two people of European descent are carriers of one gene for Cystic Fibrosis, making it the most common genetic disease in Europe. Ireland has the highest rate in the world; one person in nineteen is a carrier.
Symptoms of disease introduced by the mutations often appear in infancy and childhood and include persistent coughing, phlegm; frequent lung infections; wheezing or shortness of breath and poor growth or weight gain. Frequent greasy, bulky stools are also found and difficulty in bowel movements, and there is a deficiency in fat-soluble vitamins. Meconium ileus can occur in newborns with obstruction, abdominal distension and vomiting. The skin may taste salty. Infertility may occur in males.
The treatment for this genetic disorder is life long, and is aimed at maximizing organ function, and improving the quality of life. Targets for therapy are the lungs, gastrointestinal tract, including insulin treatment, the reproductive organs, including assisted reproductive technology and psychological support. Lung transplant is often necessary as the disease worsens.
Since 1955, the Cystic Fibrosis Foundation has driven the quest for a cure and disseminated information about the disease, the statistics of which are sobering. Cystic fibrosis is one of the most common life shortening, childhood-onset inherited diseases, occurring in one in thirty nine hundred children in the United States. Cystic Fibrosis is incurable; most patients die in their twenties and thirties, although new treatments are increasing the life expectancy to as much as fifty years. About a thousand new cases of Cystic Fibrosis are diagnosed annually; seventy percent are diagnosed by age two; forty percent of patients are eighteen or older. Finally, the median age of survival is thirty-seven years.
Ongoing research is aimed at finding new treatments to correct the defective gene and, or its abnormal protein product. The strategy of gene therapy is to bring normal copies of the gene into the airways, using nonviral, compact deoxynucleic acid. So far, changes in the chloride current have been found in the noses of patients so treated, but no other evidence of gene expression. Still, it’s a start and evidence of some small change introduced by the normal gene copies.
Other strategies are being looked at, such as normalizing the transport of salt, stabilizing mucus and improving or repairing the abnormality of the protein Natural genetic repair mechanisms mend most mutations before they become permanent.
More effective methods of managing inflammation and infection are being sought. The effectiveness of nutritional immune boosters is being explored. However, it seems that replacing the gene itself offers the best hope of the ultimate cure to cystic fibrosis sufferers.
References
Cystic Fibrosis Foundation ABOUT CYSTIC FIBROSIS
Cystic fibrosis is an inherited chronic disease that affects the lungs and
digestive system of about 30000 children and adults in the United States (70000 …
http://www.cff.org/AboutCF/
Cystic fibrosis – Wikipedia, the free encyclopedia
Cystic fibrosis (also known as CF, mucoviscoidosis, or mucoviscidosis) is a
hereditary disease that affects mainly the exocrine (mucus) glands of the lungs, …
http://en.wikipedia.org/wiki/Cystic_fibrosis
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The Merck Manual of Diagnosis and Treatment,
Seventeenth Centennial Edition: Online and In Print
Published By Merck Research Laboratories
Division of Merck & Co., Inc. Whitehouse Station, N.J.
Section 18, Chapter 247pp2006-2009
Section 19, Chapter 267pp2366-71
Copyright © 2004-2005 Merck & Co., Inc.,
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J. M. Rommens, M. C. Iannuzzi, B. Kerem, M. L. Drumm, G. Melmer, M. Dean, R. Rozmahel, J. L. Cole, D. Kennedy, N. Hidaka, M. Zsiga, M. Buchwald, J. R. Riordan, L. C. Tsui, and F. S. Collins. “Identification of the Cystic Fibrosis Gene: Chromosome Walking and Jumping.” Science 245 (4922): 1059-65 (Sept. 8, 1989). PMID: 2772657
