Cystic Fibrosis

Cystic fibrosis, also called fibrocystic disease of the pancreas, and mucoviscidosis, is a genetically deter­mined disease of infants, children, and young adults. Most of its many manifestations result from the ab­normally viscous mucus, which interferes with pul­monary function, and the insufficient production of pancreatic digestive enzymes, which causes nutri­tional deficiencies and developmental retardation.

Etiology

Among Caucasians, cystic fibrosis (CF) is the most common fatal disease having an autosomal recessive inheritance. Despite the primary involvement of sev­eral organs, the disease is caused by a single defec­tive gene that is located on chromosome 7 and is carried by about 4 percent of the Caucasian popula­tion. Its expression is similar in both sexes.

Clinical Manifestations

CF manifests itself at birth in about 8 percent of cases through mechanical obstruction of the small intestine by the secretion of abnormally viscous mu­cus (meconium ileus). Symptoms of insufficient secre­tion of exocrine (noninsulin) digestive enzymes by the pancreas appear during the first year of life in 90 percent of cases. The development of such symptoms indicates that pancreatic function is less than 10 percent of normal; and the more severe the defi­ciency of pancreatic enzymes, the more severe the fecal excretion of undigested fat, usually as diar­rhea. As much as 80 percent of dietary fat may be lost, thus partially explaining malnutrition. Loss of undigested nutrients can be corrected only partially by treatment with pancreatic enzyme tablets. Pulmo­nary disease is responsible for most of the debility and mortality. Onset occurs in the first 2 years of life in at least 75 percent of cases, and by the age of 6 years in most of the remaining cases. The initial pulmonary abnormality is obstruction of the small bronchi by abnormally thick mucus.

The sweat of a child with CF contains a concentra­tion of sodium and chloride that is about five times greater than normal, although salt is not lost exces­sively by other routes. Determining the salt content of perspiration has become a basic diagnostic test. The propensity to become salt-depleted makes per­sons with CF particularly intolerant to heat. As a result of pulmonary and metabolic therapy, many CF patients are now living into reproductive age, and thus it has been found that CF men, but not CF women, are sterile. In spite of all efforts, few pa­tients survive to age 40.

History and Geography

According to a medieval German saying, “The infant who when kissed leaves a taste of salt will not reach the first year of life.” Hence, CF was probably recog­nized many centuries ago. However, it was first iden­tified in 1936 by the Swiss pediatrician Guido Fanconi and associates, and further delineated by Dorothy H. Andersen of New York in 1938. The diagnostic perspirational salt loss was quantified by Paul di SanfAgnese and associates (New York) in 1953.

CF is most prevalent among people of central Euro­pean ancestry (1 in 2,000 to 3,000 births) and is somewhat less common in Scandinavia. Inbreeding explains incidences of greater than 1 per 1,000 in small areas. For example, the prevalence of CF among nearly 11,000 Amish in one Ohio county was more than 1 per 600, with all cases within six fami­lies, whereas there were no cases in another Amish community in a nearby county. Similar results of inbreeding have been reported from Brittany and from Afrikaners in Namibia.

The CF gene was identified in 1989. With the rapid advances in gene.transfer therapy, it may soon become possible to correct the defect from which the multiple pathological processes of this disease re­sult. Then, instead of merely prolonging life by treat­ing the symptoms, physicians may give CF infants a normal future.

Thomas G. Benedek

Bibliography

Andersen, D. H. 1938. Cystic fibrosis of the pancreas and its relation to celiac disease: A clinical and pathologi­cal study. American Journal of Diseases of Childhood 56: 344-99.

Boat, T. F., M. J. Welsh, and A. L. Beaudet. 1989. Cystic fibrosis. In The metabolic basis of inherited disease, 6th edition, ed. C. R. Scriver, et al., 2649—80. New York.

Dean, M., et al. 1990. Multiple mutations in highly con­served residues are found in mildly affected cystic fibrosis patients. Cell 61: 863-70.

Denning, C. R., S. C. Sommers, and H. R. Quigley. 1968. Infertility in male patients with cystic fibrosis. Pediat­rics 41: 7-17.

Fanconi, G., E. Uehlinger, and C. Knauer. 1936. The coeliac syndrome in congenital cystic fibrosis of the pancreas and bronchiectasis. Wiener Medizinische Wochenschrift 86: 753-6.

Gaskin, K., et al. 1982. Improved respiratory prognosis in patients with cystic fibrosis with normal fat absorp­tion. Journal OfPediatrics 100: 857-62.

Kerem, B., et al. 1989. Identification of the cystic fibrosis gene: Genetic analysis. Science 45: 1073—80.

Klinger, K. W. 1983. Cystic fibrosis in the Ohio Amish: Gene frequency and founder effect. Human Genetics 68: 94-8.

Kulczycki, L., and V. Schauf. 1974. Cystic fibrosis in blacks in Washington, D.C.: Incidence and characteris­tics. American Journal of Diseases of Childhood 127: 64-7.

SanfAgnese, P. A. di, R. C. Darling, and G. A. Perea. 1953. Abnormal electrolyte composition of sweat in cystic fibrosis of the pancreas. Pediatrics 12: 549-63.

SanfAgnese, P. A. di, and P. B. Davis. 1979. Cystic fibrosis in adults. American Journal of Medicine 66: 121-32.

Selander, P. 1965. The frequency of cystic fibrosis of the pancreas in Sweden. Acta Paediatrica Scandinavica 51: 65-7.

Wright, S. W., and N. E. Morton. 1968. Genetic studies on cystic fibrosis in Hawaii. American Journal of Human Genetics 10: 157-68.