The present data on Shwachman's syndrome diagnosed in infancy underline the possibility of improvement or normalization of exocrine pancreatic function with age, suggesting the need for periodic checks on pancreatic activity in these subjects. It also indicates the possibility of diagnosis of this syndrome in the absence of pancreatic insufficiency; decreasing frequency of infections over time; and the usefulness of early neuropsychological evaluation.

Many Cystic Fibrosis (CF) carriers have been detected testing some subjects with chronic pancreatitis for a limited number of mutations. The aim of this study was to find out if some subjects with pancreatitis and a CFTR mutation actually carry another, undetected mutation. We screened for 18 CFTR mutations plus the CFTR intron 8 poly(T) tract length a population of 67 patients suffering from idiopathic either acute, or recurrent acute, or chronic pancreatitis. Three of them were diagnosed as affected by CF. Among the others, a subset of 14 (8 CFTR mutation carriers, 4 5T carriers, and 2 sweat chloride borderliners) was selected and analyzed by denaturing gradient gel electrophoresis. Six possibly CF-related mutations were detected: L997F and 3878delG were found in two of the subjects already carrying another mutation, S1235R and L997F in one patient carrying the 5T, and L997F and D614G in the two patients with borderline sweat chloride. Among the 14 selected cases a total of 11 patients carried at least one mutation, and three of them were compound heterozygotes. Though it is debatable whether these three individuals can be considered affected by CF, their pancreatitis is possibly a clinical manifestation of some CFTR-related disease. Hum Mutat 18:166, 2001.

The diagnosis of cystic fibrosis (CF) can be difficult if the sweat test and routine deoxyribonucleic acid (DNA) analysis are inconclusive. Under these circumstances, measurement of nasal potential difference (NPD) was proposed as a complementary diagnostic tool, as demonstrated in subjects bearing the G551S or 3849+10KbC→T mutations. The purpose of the present study was to verify the diagnostic value of this technique in CF patients with a borderline sweat test. NPD was measured in 18 patients with a borderline sweat test, in whom CF diagnosis was based on the presence of one CF gene mutation in each chromosome (CF borderline). These patients were compared both to non-CF controls and CF patients with an abnormal sweat test (CF controls).Basal NPD values of CF borderline patients (mean value -39±6 mV, range -29 to -52 mV; n=18) were in the pathological range of CF controls (-39±8 mV, range -28 to -57 mV; n=37), and both were statistically different from values obtained in non-CF controls (-15±4 mV, range -6 to -23 mV; n=24; p<0.0001). Mutation analysis confirmed a high frequency of the 3849+10KbC→T mutation in this group of CF borderline patients (positive in 14 out of 18 subjects), whereas other mutations, such as ∆F508, Q552X, N1303K and R1162X, were also found to be associated with this atypical CF phenotype.These results confirm the presence of pathological values of basal NPD in CF patients with borderline sweat test, and also extend this finding to subjects bearing genotypes other than the G551S and 3849+10KbC→T mutations. The present findings, therefore, confirm the usefulness of measurement of basal nasal potential difference in all those patients in whom diagnosis of cystic fibrosis can be suspected but the sweat test remains inconclusive.