CRMS/CF-SPID
Those infants with a diagnosis of CF related metabolic syndrome (CRMS) or CF screen positive inconclusive diagnosis (CFSPID) were included in an updated guidance document from the European CF Society Neonatal Screening Working Group81. Global harmonization of the definition now has these infants referred to as CRMS/CFSPID. Some pertinent guidelines worth highlighting include, checking the CFTR2.org or CFTR-France database regarding classification and characterization of the mutation to assess for updates in classification. SC tests should be completed at initial assessment and repeated at 6 months, 2 years, and 6 years of age. At six years of age, a more extensive evaluation is recommended with lung clearance index or spirometry and chest imaging. If the results of these assessments demonstrate normal growth, lung function, imaging, and SC test <30, then it is unlikely they will convert to CF and the patient can be either a) discharged from CF care b) re-assessed again at age 14-16 years of age, or c) continue care with specialist. Further details regarding care recommendations are outlined in the publication.
Some of the most recent guidelines were informed by various research to better understand the outcomes for patients with CRMS/CFSPID. In Indiana, patients with one mutation on NBS and a SC in the indeterminate range were followed to assess overall potential for fulfilling full diagnostic criteria for CF82. Subsequent diagnosis with CF, occurred in none of the infants with a SC from 30-39 mmol/L, one out of 31 infants with SC 40-49 mmol/L, and 61% of those with SC from 50-59%. An Italian survey of centers revealed that 5.3% of the CRMS/CFSPID were re-classified over time as CF83. Specifically, in 50 infants with CRMS/CFSPID, who had early and frequent SC testing, a definitive diagnosis (CF, CF carrier, healthy infant) was found in 22% by 8.5 months, however CF was only seen in 1%83. In contrast to the Indiana data, the Italian analysis had 8 patients with a SC value between 50-59 mmol/L and only one progressed to a diagnosis of CF. A separate single center study found 6% of CRMS/CFSPID patients were reclassified as CF over the course of 12 years84. In Canada, 115 children with CRMS/CFSPID over ~7 years were assessed, and CF was diagnosed in 21%85. Those infants with a SC that was ≥40mmol/l were found to have a ten times higher hazard of having a CF converting SC level. The major message in common for these reports is the importance of clinical vigilance, repeated SC testing, and the fact that most infants will remain with a diagnosis of CRMS/CFSPID.
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