Outcomes of Infants With Indeterminate Diagnosis Detected by Cystic Fibrosis Newborn Screening

Abstract

BACKGROUND AND OBJECTIVES: Cystic fibrosis transmembrane conductance regulator-related metabolic syndrome (CRMS) describes asymptomatic infants with a positive cystic fibrosis (CF) newborn screen (NBS) but inconclusive diagnostic testing for CF. Little is known about the epidemiology and outcomes of CRMS. The goal of this study was to determine the prevalence, clinical features, and short-term outcomes of infants with CRMS. METHODS:We analyzed data from the US CF Foundation Patient Registry (CFFPR) from 2010 to 2012. We compared demographic, diagnostic, anthropometric, health care utilization, microbiology, and treatment characteristics between infants with CF and infants with CRMS.

Genotype–phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles

“…We found the p.[Arg74Trp;Asp1270Asn] complex allele in a child originally classified as CFSPID,9 44 currently asymptomatic at the age of 5 years old and in a patient with and normal SCL and CBAVD (with a residual CFTR activity on NEC of 18.9%). The p.[Arg74Trp;Asp1270Asn] complex allele has been reported only in two asymptomatic subjects so far 17.…”

Background and Epidemiology

“…The terms Cystic Fibrosis Transmembrane Conductance Regulator Metabolic Syndrome (CRMS) in the US and CF Screened Positive, Inconclusive Diagnosis (CFSPID) in Europe have been introduced to characterize the symptoms of these individuals (Table 1). 20,21 While the frequency of the diagnosis of CRMS/CFSPID depends on the NBS algorithm employed (Box 2) 22–25 both the CFF and European CF Society recommend that these individuals be followed at specialized CF centers. This population of patients is different than the patients who present clinically with some degree of CFTR dysfunction, such as congenital bilateral absence of the vas deferens (CBAVD), recurrent pancreatitis, or bronchiectasis; these patients are considered to have CFTR-related disorders (CFTR-RD) (Table 1).…”

Cystic Fibrosis: The Dawn of a New Therapeutic Era

“…NBS appears to increase the diagnosis rate of CFTR-related metabolic syndrome (CRMS); this disorder describes asymptomatic infants who have a positive CF NBS result and indeterminate diagnostic testing results. Using this CF Foundation consensus definition, 1,540 and 309 infants in the U.S. CF Foundation Patient Registry in 2010-2012 met the criteria for CF and CRMS, respectively (CF:CRMS ratio, 5:1), thus altering the dynamic makeup of the CF population (11). Even before the advent of universal NBS, the clinical phenotype of persons with CF had changed.…”