Cystic fibrosis genetic counseling difficulties due to the identification of novel mutations in the CFTR gene

Background: The Cystic Fibrosis database includes amongst the 1893 gene mutations and polymorphisms a lot of missense mutations, the disease status of which still remains unproven. In populations with high rates of CFTR mutation heterogeneity, molecular diagnosis is difficult often causing counseling difficulties especially in cases of rare and/or novel mutations. Methods: Approaches to counseling in cases of novel variants. Results: Thirty-seven novel variants (4 synonymous, 24 missense, 2 frameshift and 10 intronic substitutions) were identified and evaluated with the help of in silico tools. Conclusions: In a diagnostic environment the answers have to be given within a specific timeframe, the in silico tools in combination with the phenotype offer some help but their diagnostic value is limited and cannot be used in isolation for the determination of the severity of the mutation. © 2012 European Cystic Fibrosis Society

Wireless Capsule Endoscopy Detects Meckel’s Diverticulum in a Child with Unexplained Intestinal Blood Loss

Meckel’s diverticulum (MD) is the most common congenital anomaly of the gastrointestinal (GI) tract, affecting about 2% of the population. Most cases of Meckel’s diverticula are asymptomatic. The diagnosis of symptomatic MD is often difficult to make. We report the case of an 8-year-old boy who presented with GI bleeding due to MD. The diagnostic difficulties after an initial negative endoscopic evaluation and the diagnostic value of the various endoscopic procedures are discussed. The patient had suffered from bright red stools for 20 h before hospital admission. GI scintigraphy with 99mTc-Na-pertechnetate was negative for heterotopic gastric tissue in the small bowel area. Colonoscopy performed in order to exclude Crohn’s disease was also negative. He was placed on ranitidine at a dose of 6 mg/kg body weight twice daily. The patient remained asymptomatic over a period of 6 months before he was readmitted due to macroscopic rectal bleeding. Upper endoscopy and colonoscopy used to investigate the source of bleeding showed normal macroscopic findings. Radiolabeling of blood constituents with 99mTc on delayed imaging showed radionucleotide concentration in the ascending and transverse colon suggestive of a lesion in the ileocecal area. Further investigation with the use of wireless capsule endoscopy revealed a MD. Wireless capsule endoscopy may thus be indicated for patients with GI blood loss when other diagnostic methods, such as upper and lower endoscopy and colonoscopy, have failed to identify the source of bleeding

Longitudinal follow-up of exocrine pancreatic function in pancreatic sufficient cystic fibrosis patients using the fecal elastase-1 test

Background: A progressive decline in pancreatic function is possible in cystic fibrosis (CF) patients with exocrine pancreatic sufficiency. The secretin-cholecystokinin test is invasive and not acceptable as a repeatable procedure for children. Steatorrhea, conversely, has low sensitivity. Therefore, the aim of the present study was to evaluate the usefulness of the noninvasive fecal elastase-1 (E1) test for the longitudinal assessment of exocrine pancreatic function (EPF) in pancreatic-sufficient (PS) CF patients. Methods: One hundred eighty-four CF patients were included in the study. In all subjects, El concentrations and fecal fat excretion were measured. PS patients were followed for 5 years. Results: At the beginning of the study, 35 (19.0%) CF patients were PS, and 32 (17.4%) had normal E1 concentrations. Longitudinal measurements of E1 concentrations in PS patients with CF demonstrated stable enzyme output in 27 and gradual decrease in 8. The decrease was rapid in five infant patients and gradual in three older patients. The decrease of E1 concentrations preceded the appearance of steatorrhea in all eight subjects. Conclusions: The decline of EPF in patients with CF appears more frequently during the first months and years of life. However, late PS to pancreatic-insufficient (PI) conversion is also possible. The appearance of maldigestion is preceded by the decrease of fecal E1 concentration. Thus, the fecal E1 test is a helpful screening tool for the longitudinal assessment of declining EPF in PS patients with CF to demonstrate pancreatic deterioration. In suspected patients, fecal fat excretion should be assessed