Atypical symptoms seen in infant boy with rare CF gene mutation
Case study is example of variability in disease presentation, diagnostic challenges
An infant boy, who was first seen with recurrent infections and a failure to thrive, was diagnosed with cystic fibrosis (CF) caused by a rare genetic mutation, a case study reports.
“This case underscores the importance of considering CF even when classic symptoms are absent, as genetic mutation can lead to diverse clinical manifestations,” the researchers wrote.
The case study, “A Rare Case of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene Mutation on Exon 8 in a Patient Presenting With Recurrent Infections and Failure to Thrive,” was published in Cureus.
CF is caused by mutations in the CFTR gene, which disrupt the production or function of the CFTR protein that regulates the flow of salt and water into and out of cells. When it’s missing or dysfunctional, thick and sticky mucus builds up in various organs, including the lungs and digestive tract.
So far, more than 2,500 different mutations in the CFTR gene have been reported, the most common being F508del, occurring in about 90% of patients. CF can vary in severity, depending on the specific type of disease-causing mutation.
Rare CFTR mutation, atypical symptoms delay CF diagnosis
Here, researchers in India report on a 4-month-old boy who carried a rare CFTR mutation and presented with atypical symptoms.
The boy showed signs of failure to thrive, including poor weight gain, difficulty feeding, and mild developmental delay. He was admitted first to the intensive care unit with jaundice, a condition marked by yellowish skin and whites of the eyes. He received phototherapy for jaundice and was discharged on breastfeeding.
Although he was breastfed with intermittent top-up feeds, the boy had lost 17% of his weight since birth. An exam found a mildly swollen abdomen and an enlarged liver and spleen. Blood tests revealed elevated markers associated with liver injury. A neurological exam showed low muscle tone and poor reflexes, and he could not roll over without assistance. There were no signs of CF-related digestive problems, such as greasy stools, however.
“The absence of classic gastrointestinal symptoms initially misled the diagnostic process,” the researchers said.
The boy soon developed a high-grade fever, cough, and rhinitis, that is, inflammation of the nasal membranes. His feeding also decreased. Tests revealed a urinary tract infection and he was treated with antibiotics, but continued to lose weight.
Within a week, he developed pneumonia and was treated at the hospital for two weeks. Tests for other types of microbial infections were negative, but because he had low hemoglobin, the protein that transports oxygen in red blood cells, he was diagnosed with anemia. He was again discharged on a measured feeding schedule.
Within a week, the boy was readmitted with high-grade fever, decreased feeding, and a second urinary tract infection that was treated with antibiotics. He was tested for metabolic disorders because he had so many hospitalizations, but the results were normal. His low muscle tone and absent reflexes persisted.
A genetic analysis was performed and a mutation called p.Cys343Ter was found in both CFTR gene copies, one from each parent. The mutation, which resulted in a shorter version of the CFTR protein, was determined to cause the boy’s symptoms.
The boy died from recurrent infections before more tests could be conducted, including the standard sweat chloride test to confirm CF.
“This case exemplifies the variability in cystic fibrosis (CF) presentations and underscores the diagnostic challenges associated with atypical cases,” the researchers wrote.
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