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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