WBR0117
| Author | [[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D. and Rim Halaby, M.D. [1])]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Pathophysiology |
| Sub Category | SubCategory::Gastrointestinal |
| Prompt | [[Prompt::A married couple with strong positive family history for cystic fibrosis undergoes genetic testing. While neither the man nor his wife has cystic fibrosis, genetic tests reveal that both are carriers for the ΔF508 mutation. The couple refuses in vitro fertilization (IVF) in favor of a natural pregnancy. Which of the following is the most likely manifestation of cystic fibrosis among neonates?]] |
| Answer A | AnswerA::Cyanosis |
| Answer A Explanation | [[AnswerAExp::Neonates with tetralogy of Fallot often present with blue baby syndrome.]] |
| Answer B | AnswerB::Fever |
| Answer B Explanation | [[AnswerBExp::Patients with cystic fibrosis are not at a particular increased risk of neonatal meningitis, which is usually caused by Streptococcus agalactiae (Group B Streptococcus or GBS), E. coli, and Listeria monocytogenes.]] |
| Answer C | AnswerC::Vomiting |
| Answer C Explanation | [[AnswerCExp::Meconium ileus is defined as failure of a neonate to pass its first stool within 48 hours. It is caused by an obstruction of the ileum. Meconium ileus results in the formation of thickened colonic mass that results in abdominal distension and bilious vomiting following birth.]] |
| Answer D | AnswerD::Seizure |
| Answer D Explanation | [[AnswerDExp::Patients with neonatal meningitis may present with seizures. The list of differential diagnoses of neonatal seizures is long; it includes neruological disesaes, infectious diseases, and mitochondrial diseases, among many others. Patients with cystic fibrosis, however, do not typically present with neonatal seizures.]] |
| Answer E | AnswerE::Jaundice |
| Answer E Explanation | [[AnswerEExp::Patients with cystic fibrosis might suffer from neonatal jaundice, but this is not the most likely presentation. Neonates wtih cholestatic disease, duodenal atresia, hemolysis, infections, and congenital hypothyroidism may typically present with jaundice.]] |
| Right Answer | RightAnswer::C |
| Explanation | [[Explanation::Cystic fibrosis is an autosomal recessive genetic disease that is most commonly caused by a defective CFTR stemming from a deletion of phenylalanine residue at positive 508. Cystic fibrosis results in abnormal chloride transport due to a non-functional chloride channel, termed "cystic fibrosis transmembrane conductance regulator" (CFTR). Normally, the apical sodium channels reabsorb sodium across the ductular lumen. This phenomenon is followed by the reabsorption of chloride counter-ion using CFTR. Patients with cystic fibrosis have abnormal CFTR that limits the reabsorption of sodium and chloride. As such, the hallmark of cystic fibrosis is formation of highly concentrated (salty tasting) sweat.
Patients with cystic fibrosis suffer from symptoms caused by mucosal obstruction. Thick secretions in the lungs block the narrow distal airways and submucosal glands, causing the formation of neutrophil-dominant mucopurulent debris with peribronchiolar inflammation, glandular hyperplasia, and scar tissue. In the pancreas, mucus accumulation and obstruction result from a reduced flushing capacity of the pancreatic ducts due to failure to release anions across the cellular membranes. Similarly in the intestines, abnormal chloride secretion leads to hyperviscous secretions and results in intestinal obstruction. Approximately 10% to 15% of neonates with cystic fibrosis manifest with meconium ileus, characterized by failure to pass the first stool within the first 48 hours. Intestinal obstruction is usually followed by abdominal distention and bilious vomiting. In addition, rectal prolapse (protrusion of the internal rectal membranes) is common and is associated with increased fecal volume, malnutrition, and increased intra-abdominal pressure. |
| Approved | Approved::No |
| Keyword | WBRKeyword::Cystic fibrosis, WBRKeyword::CF, WBRKeyword::Meconium ileus, WBRKeyword::Bilious vomiting, WBRKeyword::Vomiting, WBRKeyword::Intestinal obstruction, WBRKeyword::Obstruction, WBRKeyword::Neonate, WBRKeyword::Newborn, WBRKeyword::Genetic, WBRKeyword::Genetics, WBRKeyword::Complication, WBRKeyword::Chloride, WBRKeyword::Channel, WBRKeyword::CFTR, WBRKeyword::Autosomal, WBRKeyword::Recessive, WBRKeyword::Autosomal recessive |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |