The report, “Uncommon clinical presentation of cystic fibrosis in a patient homozygous for a rare CFTR mutation: a case report,” was published in the journal BMC Pediatrics.
Newborn screening (NBS) can be used to diagnose CF early in life, allowing treatments to start before obvious symptoms develop. Typically, this screening involves measuring a blood marker, called immunoreactive trypsinogen (IRT), in the first week of life.
Following positive results from this test (IRT usually is elevated in CF patients), newborns can be referred for confirmatory testing, which often involves measuring the amount of chloride ions in sweat and genetic testing for mutations in the CFTR gene (defective in CF patients).
In some cases, the results of NBS are not enough to either confirm or refute a diagnosis of CF, particularly in instances of abnormal clinical presentation and/or rare CFTR mutation(s).
“Despite all knowledge and modern diagnostic tools at our disposal, sometimes the clinical presentation is so inconclusive, that making a final diagnosis remains a challenge,” the researchers wrote.
The new report describes the case of a 1-year-old in Poland whose diagnosis was a challenge.
At two months of age, the infant was hospitalized due to an infection in the upper respiratory tract. Two weeks later, the boy was hospitalized again due to poor weight gain and vomiting.
The initial NBS revealed elevated IRT levels indicative of CF. However, analysis of the patient’s sweat provided unclear results; of four individual measurements, only one was indicative of CF. The initial genetic test also screened for more than 700 CF-associated mutations, and the patient was negative for all of them.
The boy received anti-bacterial and anti-fungal medications to control a suspected lung infection, though this did not have notable clinical benefits. The patient was fitted with a nasogastric feeding tube (a tube through the nose to the stomach) to allow for adequate nutrition.
Further testing, including analysis of the patient’s urine, were suggestive of a metabolic disorder, but no definitive results were obtained. The patient also was found to be anemic, and to have abnormal fluid accumulation in the body (edema).
Sweat tests were repeated, using multiple methodologies, and the results were positive for CF. Further metabolic workup also excluded conditions other than CF. Moreover, the patient’s CFTR genes were completely sequenced, revealing identical mutations (dubbed c.4035_4038dupCCTA) in both copies of the gene (one inherited from each biological parent, neither of whom had symptoms of CF).
After several months of holistic treatment, including a high-protein diet and pancreatic enzyme replacement therapy, the patient’s growth (weight and length) was more in line with typical developmental milestones.
Overall, this patient’s journey to diagnosis was hindered by numerous factors, the researchers wrote. First the abnormal clinical presentation, which was further complicated by ambiguous results from laboratory tests, including both metabolic profiling and sweat chloride analysis.
“Sweat test measurements performed in better nutritional status and without peripheral [edema] were highly positive in this patient,” they wrote, suggesting a need to account for these factors in early testing.
Negative genetic tests also were a complicating factor. The team noted that the initial genetic testing “excluded 86% of mutated CFTR gene alleles in the Polish population.”
Moreover, the detected mutation is quite rare, having been reported previously in only Polish individuals, and only in combination with other CF-related mutations.
The team concluded that “the reported case shows the unusual presentation of the disease,” and suggested that the “patient’s clinical symptoms and laboratory findings, in combination with molecular test results, provide useful information for further observation of genotype-phenotype [genetics and disease presentation] correlations in cystic fibrosis.”
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