Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
Multiplexing homocysteine into first-tier newborn screening mass spectrometry assays using selective thiol derivatization
We previously published about this research in a story titled “Researchers Develop New Homocystinuria (HCU) Screening Test” which can be found here. The study was originally published in the research journal Clinical Chemistry. You can read the full text of the study here.
This research team was affiliated with the Centers for Disease Control and Prevention (CDC).
What Happened?
Homocystinuria (HCU) is a congenital disease that can have dire consequences if not treated in a timely manner. Because of the risk of devastating impacts, the Department of Health and Human Services has had the disease on a list of conditions that are recommended for newborn screening. However, the screening method used today is limited in effectiveness. This method measures levels of methionine. While this is a useful indicator of the disorder, methionine levels take time to rise and may be within the normal range in newborns when screening occurs.
As a result, up to half of homocystinuria cases may be missed by the newborn screening test, meaning that many patients risk going too long without proper treatment. The research team in this study sought to develop a new screening method that would be able to detect the condition with greater accuracy in newborns. The new testing approach measures levels of homocysteine instead of methionine. In newborns with the disorder, homocysteine levels increase more rapidly than methionine levels do. They almost always increase during the first few days of life, when newborn screening is performed.
The performance of this testing method was evaluated using screening samples from babies that had already been diagnosed. 100 were from healthy babies, 50 were from HCU-negative infants getting total parenteral nutrition (TPN, commonly given to babies in the NICU), and two were from babies that were HCU-positive. The test was able to distinguish between the positive and negative samples, as well as between the babies receiving TPN and the HCU-positive samples.
This final point is important because another weakness of the old test was that it could produce false-positive results in infants receiving TPN. Overall, this simple change will result in a test that gives far more accurate results and should be able to detect virtually all cases, which is a stark difference from the old newborn screening method.
About Homocytinuria (HCU)
Homocystinuria is a rare genetic disorder in which a deficiency of an enzyme called cystathionine beta synthase leads to inhibited metabolism of an amino acid called methionine. Deficiencies affecting folate and vitamins B6 and B12 can also cause symptoms to appear. The disorder can lead to major signs and symptoms affecting multiple body systems. These symptoms include various eye problems (myopia, glaucoma, optical atrophy), abnormal chest shape (pectus excavatum or carinatum), vascular disease (thrombosis, atheroma), psychiatric problems, flushed cheeks, seizures, and intellectual disability. Patients often have a thin, tall build, high arched feet, knock knees, and long limbs. There is no known cure for homocystinuria, with many interventions being symptomatic and supportive. Around half of patients appear to benefit from high doses of vitamin B6, and continue this supplementation for life. Other options include a diet low in sulfur and protein, cysteine and folic acid supplementation, and trimethylglycine. To learn more about homocystinuria, click here.
Why Does it Matter?
The development of a more accurate newborn screening test for homocystinuria means that outcomes for patients are likely to improve significantly, as more babies will get diagnosed in time to receive proper treatment. This will help them avoid potentially severe symptoms of the disorder, such as intellectual disability and seizures.
“Here we present the only flow injection analysis-tandem mass spectrometry first-tier newborn screening method that directly quantifies total homocysteine from dried blood spots. The ability to screen total homocysteine during first-tier newborn screening is a significant step toward reducing HCU false-negative rates, which will enable early identification and intervention to reduce HCU-associated morbidity and mortality.” – Konstantinos Petritis, Ph.D., CDC
