HCU Network America & the Classical Homocystinuria Stakeholder Community Urge State Newborn Screening Labs to Revise Screening Protocols for Classical Homocystinuria to Ensure Fewer False Negative Screening Results & Delayed Diagnoses.

We, the undersigned, urge State Newborn Screening Laboratories across the United States to review and revise screening protocols for Classical Homocystinuria (HCU) to ensure fewer false negative screening results & delayed diagnoses. Our message to state laboratories is as follows:

Data suggests that, currently, up to 50% of babies born with Classical HCU are being missed, receiving false negative results that can have a devastating impact on them.

HCU is a genetic disorder of the metabolism in which individuals are born with abnormalities in both copies of the Cystathionine Beta Synthase (CBS) gene. A rare and potentially serious inherited condition, HCU prevents the body from breaking down certain amino acids, the building blocks of proteins, causing a harmful build-up of substances in the blood and urine that can have severe and potentially life-threatening consequences. Thankfully, because of newborn screening, we have been able to identify many individuals and provide preventive treatment early in life when it is most effective and before symptoms develop. Newborn screening involves a heal prick to gain a small blood spot after babies are born to test for many serious treatable conditions. However, although HCU officially became part of the US Recommended Uniform Screening Panel (RUSP) in 2009, issues with screening protocols continue to result in missed cases.

US and international experts in newborn screening for HCU have recommended that labs use a more precise measure of the amino acids that dangerously build up in babies with HCU, lowering cut-off for the methionine (MET) and/or a corresponding ratio of MET to Phenylalanine (PHE). The lower cutoff for MET can range from 39 to 50 µmol/L, depending on lab median. Additionally, experts recommend a second-tier test for total homocysteine (tHCY) using the same blood spot. The CDC is finalizing a second-tier assay for tHCY that will be made available to the state labs.

Through compelling evidence recommended by Classical Homocystinuria experts, by taking these steps, your state would both significantly lower the number of false negatives and increase the likelihood of identifying HCU in newborns. We urge each state newborn screening lab to consider the latest recommendations by experts to revise current protocols and prevent more serious HCU consequences for patients in your state. People with HCU need and deserve to be diagnosed as newborns so that they have a better chance at living healthier, happier lives.