Reaching the diagnosis of cystic fibrosis - the limits of the spectrum

Background: Cystic fibrosis is the most common life-autosomal recessive gen etic disorder in Caucasians. Typically it is a multisystem disease diagnose d by increased chloride levels on sweat testing, with mortality mainly to p rogressive respiratory disease. The clinical spectrum of CF has recently be en much expanded. Genetic testing for mutant CF transmembrane regulator has revealed atypical cases where sweat test results are borderline or normal. In other patients, genetic mutations cannot be identified but abnormal CFT R function is shown using nasal potential difference measurement. Objectives: To highlight the diagnostic and therapeutic dilemmas in cases o f atypical cystic fibrosis. Methods: We reviewed patients with atypical CF and widely varying phenotype who are managed at Schneider Children's Medical Center of Israel. Results: Two patients had severe lung disease but little expression in othe r organs. Accurate diagnosis was essential to enable aggressive therapy in a specialized center. Four other patients are in excellent general health b ut have Symptoms limited to male infertility, heat exhaustion, pancreatitis or transient liver dysfunction, while lung disease is minimal. For these p atients, careful counseling is needed to avoid unnecessary upheaval, inappr opriately aggressive management, and the psychosocial implications of a CF diagnosis. These dilemmas have increased considerably in our center, as in others worldwide. Conclusion: It is our obligation as clinicians - at the level of both prima ry physician and referral center - to maintain an ever higher index of susp icion for CF, tempered by a rational program of counseling and management a ppropriate to the individual.