CFTR-Related Metabolic Syndrome (CRMS)
CFTR-related metabolic syndrome (CRMS) is a relatively new condition identified because of advances in the newborn screening process for cystic fibrosis (CF).1,2 CRMS is sometimes referred to as "atypical cystic fibrosis."
Cystic fibrosis is an inherited disease caused by a gene mutation that is carried by both parents. CFTR, the Cystic Fibrosis Transmembrane Conductance Regulator, is a protein made by the CF gene. This protein helps moves salt (chloride) in and out of the cells in the body. When salt isn’t transported normally, an excessive amount of mucus can build up in the lungs and pancreas.1 CF develops when both of the CFTR genes have mutations.1,3
People with one gene are typically carriers and do not develop the disease. CRMS categorizes infants with inconclusive sweat tests (that measure the level of salt in sweat) and DNA test results who are at risk for developing some of the same symptoms and health problems as someone with CF.1
CFTR-related metabolic syndrome diagnosis
CRMS is most often identified as a result of newborn screening for cystic fibrosis (CF). The advances in and widespread use of newborn screenings have now permitted the routine diagnosis of asymptomatic children.2 All 50 states now have routine newborn screenings for cystic fibrosis.
When a CF screening test is abnormal, but the results do not meet the full criteria for cystic fibrosis, CRMS may become the diagnosis.1,3 It is a condition that is considered to have a milder form of CFTR dysfunction.3 The range of test values used to make a diagnosis vary across the United States and Europe; leading to some variation in the reported incidence of CRMS.2
For those children who were not identified by way of a newborn CF screening, but received similar test results later, the same condition is called CFTR Related Disorder and not CRMS.1
CF screenings at birth are done with a blood test from a heel prick. Later on, a sweat test is performed to measure the level of chloride present. If the results are between normal levels and CF levels, the results are labeled intermediate, and a person is considered to have CRMS or CFTR-related disorder. These children are at an increased risk of developing health issues that are common in cystic fibrosis, including digestion, lung, sinus, and fertility problems.1
CF can cause health problems, particularly with the pancreas and intestines. This impacts the effectiveness of digestion, resulting in malabsorption of nutrients needed for growth and development.1 Thick mucus blocks the flow of pancreatic enzymes necessary to digest fats and proteins. It affects the lining of the lungs and airways, making breathing more difficult and leaving individuals likely to develop lung and sinus infections.1
The reason some people develop CFTR-related metabolic syndrome is not clearly understood.1 Anyone diagnosed with CRMS should see a CF medical specialist to have regular evaluations so that medical issues can be detected early and treated effectively. Researchers are still evaluating which children with CRMS will go on to develop cystic fibrosis disease.1,2 There are no definitive guidelines on the classification and treatment of people who have 2 CFTR mutations but no CF symptoms, or normal sweat chloride test levels, or one CFTR gene mutation and intermediate sweat chloride test results.2
Since the majority of people now diagnosed with CF and its related syndromes are infants, identified during newborn screenings more long-term research is needed to better define who should receive treatment and when. If screening values for CF and CRMS are globally standardized, then the reported incidence, appropriate education, medical monitoring, and treatment can be more uniform.4
When is it time to seek advice?
Knowing the physical symptoms of CF can help you identify significant changes in your child. Make an appointment to see your doctor if your child is:1