• Sign Our Petition to show your support for NBS revisions!
• Review our Educational and Advocacy resources to learn more about the issues surrounding HCU NBS!

HCU Network America asks you to evaluate your current process and consider lowering your MET cut-off (if higher than 39 to 50 uM) and/or a corresponding ratio of MET to Phenylalanine (PHE) & instituting second-tier testing for tHCY.  The full process, rationale, and benefits can be found here. If laboratory resources are not available to implement a second-tier test for tHCY, please reach out to HCU Network America’s Executive Director, Danaé Bartke, at dbartke@hcunetworkamerica.org; Danaé can help identify potential labs to which you could consider outsourcing second-tier tests.

CDC's Newborn Screening and Molecular Biology Branch developed and validated a novel assay which multiplexes homocysteine in a first-tier newborn screening method along with other biomarkers. Homocysteine is more specific for screening homocystinuria (HCU) than the currently used biomarker, methionine. This novel assay can significantly improve HCU detection in newborns." Carla Cuthbert,

We urge you to alter your process even if you believe you have not missed any HCU patients; our community has reported delayed diagnoses and unfortunately, some states do not have an ideal reporting system to ensure that there is a full accounting of patients who may have been missed by NBS.  Your willingness to proactively take action could lead to improved lives for many HCU patients and their families. Please read Elliott’s story below to see the impact of his delayed diagnosis:

At two years old, Elliott was diagnosed with Homocystinuria, a rare genetic metabolic disorder. Being missed in his newborn screening test led to a delayed diagnosis for Elliot and resulted in nearly losing him to this treatable disease. He spent 29 days in the ICU with blood clots in the brain, and he had a stroke. Had we known at birth that he had this treatable disorder, we could have avoided a lot of suffering. I’ve since learned that his methionine level at birth was 44, and the cutoff in our state is 65. I urge South Carolina and other states to lower their MET cutoffs to identify all babies with classical HCU at birth.

— Liz Carter, parent to HCU patient Elliott, diagnosed at 2.5, South Carolina 

Ways to Get Involved

• Contact Danaé Bartke, HCU Network America Executive Director, at dbartke@hcunetworkamerica.org for the following:
  • Schedule a 1:1 conversation about your state and how we can help you identify and incorporate the right revisions to your screening protocols.
  • If your lab has already optimized screening and you wish to be a peer-to-peer mentor, provide a case study, or share your story to encourage other states to make changes.
• If your state provides second-tier testing, please help us gather input here.
• Watch our webinar – Classical Homocystinuria: A Journey to Improve Outcomes Through Newborn Screening (2022) for more information and tell us how we can help you to enact change.

The Importance of Missed Diagnosis Reporting

"The Colorado Newborn Screening Laboratory went from a methionine cutoff of 100 to 48. Not long after making the change, a missed HCU case was reported on a 2-year-old. When their newborn screen was audited, they had a methionine value of 53. This screening revision emphasizes the importance of missed diagnosis reporting – communicating an accurate and timely diagnosis to patients is imperative for providing accurate and quality care. It is critical for people living with rare and undiagnosed diseases to have a timely and accurate diagnosis."

Greg Bonn MT(ASCP)
Newborn Screening Program Manager
Colorado State Public Health and Environment Laboratory
Division of Disease Control and Public Health Response (DCPHR)

• Fill out the Survey on Homocystinuria Patients Missed by NBS & share it with your colleagues and professional networks.
• Contact your state/region’s NBS lab to engage them in the HCU NBS conversation, and advocate for an improved process through the following dialogue:
  • What is our state’s MET cut-off?
  • Has the lab considered the benefits of using a lower MET cut-off (if higher than the recommended levels, e.g. 39 to 50 uM)
  • Do the cut-offs vary by weight, length, or gestation period? Male or female?
  • Does our state use a MET/PHE ratio?
  • Are there other biomarkers/analytes that you are looking at when diagnosing HCU?
  • Have you considered using CLIR to aid in the interpretation of NBS results?
  • Does our state have a routine 2^nd NBS test?
    • When is the test administered?
    • Are the cut-offs the same?
  • Does our state have a second-tier test for tHCY?
    • If so, what cut-off do you use to trigger the second-tier test?
  • Would you advocate changing the process to ensure we diagnose as many HCU patients at birth as possible?
    • Is there a committee on NBS within your state you need to work with to get support for this change?
  • Would the lab staff like to talk to an expert who is implementing the recommended two-tier process? Would they be willing to outsource the second-tier test if resources are not available?
    • If so, please contact HCU Network America’s Executive Director, Danaé Bartke, at dbartke@hcunetworkamerica.org

• Sign up for our monthly newsletter, the HCU Herald here!
• Please share our newborn screening survey with your clinic
• Be an advocate for change in your state. Fill out the form here!
• Share your HCU Newborn Screening Story. Fill out the form here!