What Is CRMS?
CRMS stands for cystic fibrosis transmembrane conductance regulator (CFTR)-related metabolic syndrome. This is a term doctors use when a CF diagnosis is inconclusive after newborn screening and a sweat test. In Europe, doctors use the term CF screen positive, inconclusive diagnosis (CFSPID). CRMS is the term used in this article.
A CF diagnosis is typically confirmed with a sweat test. The sweat test measures salt in sweat:
- Under 30 is normal
- Between 30 and 59 is called intermediate
- 60 and over usually means CF
Infants with CRMS have a newborn screening that is positive for CF but have sweat test results that fall within the middle range. To meet CRMS criteria, the baby must have a positive newborn screening test for CF, and then meet the criteria for either Option A or Option B below.
Option A:
- Sweat test (salt level): less than 30 mmol/L (low)
- CFTR gene changes: 2 gene mutations, and doctors are not sure what at least 1 of them means yet
Option B:
- Sweat test (salt level): 30–59 mmol/L (middle range)
- CFTR gene changes: 0 or 1 gene mutation that is known to cause CF
What causes CRMS?
CF is caused by a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To have cystic fibrosis, a child must inherit one copy of the CFTR gene mutation from each parent.
In CRMS, a baby has two CFTR mutations, but one of them may not be known to cause CF.
Learn about the CF Foundation’s CRMS guidelines.
What Does CRMS Mean for Your Child?
Your baby does not have cystic fibrosis. CRMS is not a disease. It means your baby had a positive screening but does not have CF. Most babies with CRMS stay healthy.
"Because of the limited knowledge, we must rely on clinical evidence to assess our daughter’s evolution. Our annual check-ups at Children’s Hospital are always a brutal reminder of the threat that looms ... And, yet, we know we are fortunate. Our daughter is growing up without any symptoms that would make us think that the CRMS potential threat is manifesting in any way." — Álvaro La Parra-Pérez, parent of a child with CRMS, from the CF Community Blog
Monitoring and Follow-Up
Regular checkups are important for children with CRMS. Your child should see a CF specialist at a CF Foundation-accredited care center at least once a year until at least age 8, or as advised by the care center team. At these visits, the CF care team will check your child’s height and weight and do a sweat test. The CF team may also ask you about any emotional stress you and your child may be experiencing related to CRMS.
Your child should see their regular doctor and a CF specialist as soon as possible if your child has any of these symptoms:
- No weight gain
- Loose stools, very bad gas, or constipation that lasts more than two weeks
- Very bad stomach aches
- Coughing or wheezing that lasts more than two weeks
A very small number of babies with CRMS may develop CF later. There are two main ways a CRMS diagnosis would change to CF as a child grows:
- A child with CRMS develops symptoms that seem like CF. The most common symptom of CF is a persistent cough. If your baby has a cough that lasts for more than two weeks, contact your pediatrician or the CF care team.
- A repeat sweat test shows there is more salt in the sweat. Sweat tests should be repeated yearly or at intervals recommended by the CF team. Yearly monitoring is important.
Possible CFTR-Related Disorders
Some people with CRMS may develop conditions like sinus infections, asthma, constipation, or pancreatitis later in life. These conditions, called CFTR-related disorders, are not CF, but they are more common in people who carry an abnormal CFTR gene.
The most common CFTR-related disorders are absence of the vas deferens (a cause of infertility in men) and pancreatitis.
- Absence of the vas deferens means the sperm canal is missing. But men with this condition still make normal sperm and are able to have children through assisted fertilization, commonly known as IVF.
- Pancreatitis can cause severe stomach pain. There are tests for pancreatitis. It is important to tell a doctor about your child’s CRMS if they have severe stomach pain.
It is important to keep your child’s CF team updated about any health conditions that develop.
Family and Genetic Counseling
Because CF is genetic, your baby’s results may also matter for your family. CRMS is a label used after newborn screening, so it isn’t something older relatives would be “diagnosed” with. However, family members could be CF carriers or, less commonly, have CF or a CFTR-related disorder. A genetic counselor can explain what these results mean, the chances that a future child could have CF or receive a CRMS label during newborn screening, and whether family members may want to get tested.
Support From Your Care Team
Although most children with CRMS never develop CF, parents can find the uncertainty emotionally stressful. Your CF team is here to support you through this. Everyone copes in their own way when their baby is diagnosed with CRMS. Contact your CF team for support when you need it.
The CF Foundation is committed to understanding more about CRMS/CFSPID through continued research and improvements in clinical care.
