Case Report: Japanese Siblings of Cystic Fibrosis With a Novel Large Heterozygous Deletion in the CFTR Gene

Cystic fibrosis (CF) is a rare disease in the Japanese. The most common CFTR variant in Japanese CF patients is a large heterozygous deletion that can easily avoid detection by standard gene sequencing methods. We herein report a novel large heterozygous deletion in the CFTR gene in Japanese siblings with CF. A genetic analysis was performed in two patients (9-year-old boy and 5-month-old girl) who were clinically diagnosed with CF because of the positive result for the rapid fecal pancreatic elastase antigen test and the elevation of the sweat chloride concentration. In addition to conventional polymerase chain reaction (PCR) and direct sequencing, multiplex ligation-dependent probe amplification (MLPA) was performed to check for a large deletion and duplication of the CFTR gene. Based on MLPA findings, the breakpoint of heterozygous deletion was identified by real-time quantitative PCR followed by the sequence of the amplified junction fragment. In MLPA, the numbers of the fragments corresponding to exons 1, 16, 17a, and 17b and 234 nt and 747 nt upstream from the translation initiation codon of exon 1 in the CFTR gene and exon 3 in the ASZ1 gene were reduced by almost half. The c.2908+1085_3367+260del7201 variant (exon 16-17b deletion) was identified in one allele. The other allele had a large 137,567-bp deletion from g.117,361,112 (ASZ1 3′ flanking region) to g.117,498,678 (CFTR intron 1) on chromosome 7. Since the deletion variant lacked the entire promoter region of CFTR, CFTR mRNA would not be transcribed from the allele, indicating it to be a novel pathogenic variant causing CF. As large mutations are frequently detected in Japanese CF patients, MPLA can be useful when searching for variants.

Digestive enzyme replacement relieves growth failure in preterm infants with poor exocrine pancreatic function: a retrospective case series

In orally fed preterm infants, poor weight gain may be linked to low fecal pancreatic elastase-1 (FPE-1) activity, indicative of exocrine pancreatic insufficiency. The objective of this study was the retrospective assessment of the effect of exogenous digestive enzyme replacement by gavage in preterm infants with growth failure and low FPE-1 (<200 μg/g). We analyzed weight gain relative to baseline and caloric intake during 14-day periods before and after institution of digestive enzyme replacement containing 6000 U lipase and 240 U protease kg−1 d−1. Among 46 of 132 preterm infants < 1250g birth weight surviving to at least 14 days in whom FPE-1 was determined, 38 infants had low FPE-1 (< 200 μg/g), and 33 infants received exogenous digestive enzyme replacement. Average daily weight gain significantly increased from 14.4 [range 2.6–22.4] g kg−1 d−1 to 17.4 [8.4–29.0] g kg−1 d−1 (P = 0.001), as did weight gain per kcal, from 0.08 [0.02–0.13] g kcal−1 d−1 to 0.11 [0.05–0.18] g kcal−1 d−1.Conclusion: In preterm infants with signs and symptoms of exocrine pancreatic insufficiency, exogenous digestive enzyme replacement is associated with improved growth. What is Known:• Very preterm infants on full enteral nutrition may display growth failure linked to transient poor exocrine pancreatic function.• Porcine pancreatic enzymes covered with an acid-resistant coating are too large to pass the internal diameter of most gavage tubes used in very preterm infants.What is New:• Administration of a liquid formulation of acid-resistant microbial digestive enzymes in preterm infants with growth failure and low fecal pancreatic elastase-1 values was associated with improved weight gain.• Response to exogenous digestive enzyme replacement was associated with the prior extent of growth failure.

Influence of SPK with Enteric Drainage on the Pancreatic Exocrine Function in Diabetic Patients with Uremia

Objective. This study aimed to determine the use of fecal elastase in evaluating the effect of simultaneous pancreas–kidney transplantation with enteric drainage on the pancreatic exocrine function of diabetic patients with uremia.Methods. A total of 19 patients with simultaneous pancreas–kidney transplantation (SPK) with enteric drainage, 31 diabetic patients with uremia (chronic renal failure (CRF)), 22 diabetic patients with uremia who underwent renal transplantation (RT), and 20 normal individuals (CON) were included in the study. Pancreatic exocrine insufficiency was determined using fecal elastase. Results. The fecal pancreatic elastase level in SPK patients with enteric drainage was 479 μg/g, which was significantly higher than 229 μg/g in CRF patients and 197 μg/g in RT patients. Using 200 μg/g as the established threshold, a reduced fecal pancreatic elastase level was found in 14/31 of CRF patients, 12/22 of RT patients, 1/19 of SPK patients with enteric drainage, and 1/20 of CON patients. The correlation analysis revealed a significant association between fecal elastase and glycosylated hemoglobin.Conclusions. The present study indicated that SPK with enteric drainage improves pancreatic endocrine and exocrine functions. Fecal elastase may be a clinically relevant means to determine the therapeutic effects.

Changes in gepatopancreatobiliary system organs and quality of life in patients after cholecystectomy

Aim. To assess the condition of hepatopancreatobiliary system and quality of life in patients in the remote period after cholecystectomy.Methods. 88 patients with cholelithiasis who undergone cholecystectomy in 2008-2010 were examined 5 years after the surgery. Common blood count, blood biochemistry test were performed, fasting blood glucose level was measured, esophagogastroduodenoscopy, ultrasonic examination of abdominal organs, fractional duodenal intubation, fecal elastase test (ELISA, «BioServ Diagnostics», Germany) were performed. Patients filled out questionnaires to assess the quality of life: MOS SF-36 (Medical Outcomes Study Short Form), GIQLI (Gastrointestinal Quality of Life Index) before, 1 and 5 years after cholecystectomy.Results. According to the esophagogastroduodenoscopy, 56 (63.6%) patients had duodenal reflux, 21 (23.8%) - duodenal diverticula, 9 (10.2%) - reflux esophagitis. Reduced fecal pancreatic elastase-1 was detected in 37 (42%) of patients. According to the fractional duodenal intubation, hypersecretory type was the most prevalent, 40 (45.5%) patients had hypotonic sphincter of Oddi, 48 (54.5%) - hypertonic sphincter of Oddi. All patients had crystals of calcium bilirubinate, leukocytes and bacteria in bile, microliths were identified in 76 (86%) of patients. After emergency surgery, quality of life increased by all indicators, after planned cholecystectomy for asymptomatic cholelithiasis the quality of life decreased 1 and 5 years after cholecystectomy. After planned cholecystectomy for symptomatic cholelithiasis, the surgery improved quality of life, but after 5 years indicators for quality of life returned to preoperative levels.Conclusion. Various changes in hepatopancreatobiliary system organs are detected in patients after cholecystectomy, like disorders of bile formation and biliary excretion, sphincter of Oddi dysfunction, decreased function of the pancreas, which reduce the quality of life.