Lethal course of meconium ileus in preterm twins revealing a novel cystic fibrosis mutation (p.Cys524Tyr)

Abstract

Background: In term newborns meconium ileus is frequently associated with cystic fibrosis. Reports on meconium ileus in preterm infants being diagnosed with cystic fibrosis early after birth are very scarce. Associations between genotype and phenotype in cystic fibrosis and its particular comorbidities have been reported.

Case presentation: Two extremely preterm twin infants (26 weeks of gestation) born from a Malaysian mother and a Caucasian father were presented with typical signs of meconium ileus. Despite immediate surgery both displayed a unique and finally lethal course. Mutation analysis revealed a novel, probably pathogenic cystic fibrosis mutation, p.Cys524Tyr. The novel mutation might explain the severity of disease next to typical sequelae of prematurity.

Conclusion: Preterm neonates with meconium ileus have to be evaluated for cystic fibrosis beyond ethnical boundaries, but may take devastating clinical courses despite early treatment. The novel, potentially pathogenic CF mutation p.Cys524Tyr might be associated with severe meconium ileus in neonates. Disease-modifying loci are important targets for intestinal comorbidity of cystic fibrosis.

Figure 1

Initial X-rays of both twins. Chest and abdominal X-ray with contrast agent upon initial presentation of twin I (a) and II (b) showing contrast agent stopping at the inflated, distended small intestine next to signs of neonatal respiratory distress syndrome.

Figure 2

Autopsy findings of twin I (histology). Pancreatic tissue shows distinctive PAS-positive intraductal mucous masses (♦) and dilatation of the pancreatic ducts (rectangles). PAS staining, A 10×, B 20×. Consistent with meconium ileus the large intestine is filled with densely packed stratified mucus (●) while the mucosa is flattened (▲). PAS staining, C 4×, D 10×.

Figure 3

Abdomen of twin II after repeated unsuccessful surgery.