Newborn Screening for Alpha-Thalassemia in the United States: A 2016 Survey

Alpha-thalassemia is a group of inherited disorders in which the body makes too little of the alpha chain of hemoglobin. Depending on the genes involved, it can cause moderate to profound anemia, breakdown of red blood cells, growth delays, an enlarged spleen and a higher risk of blood clots, and some patients need regular transfusions. About 5% of the world’s population carries an alpha-thalassemia variant, making the thalassemias the most common single-gene disorders. National U.S. data are lacking, but in California about 1 in 10,000 newborns has an alpha-thalassemia syndrome. It is most common among people of Laotian and Cambodian descent, and also occurs in people of African, Chinese, Filipino, Mediterranean, Vietnamese, Thai and Middle Eastern ancestry.

Screening by another route

Alpha-thalassemia is not a core condition on the U.S. Recommended Uniform Screening Panel for newborns. But the methods programs use to screen for sickle cell disease, which is on the panel, also detect hemoglobin Bart’s, an abnormal hemoglobin whose level tracks the severity of alpha-thalassemia: the more alpha genes deleted, the more Hb Bart’s and the more severe the disease.

Using a different testing platform for the second round of screening than the first catches the most newborns with telltale Hb Bart’s levels, because platforms differ in sensitivity.

The survey

In October 2016, the Association of Public Health Laboratories’ Hemoglobinopathy Workgroup sent the first nationwide survey on the subject to all 53 U.S. newborn screening programs. 44 (83%) responded — together with four non-responding programs that send specimens to responding ones, covering 86% of U.S. births.

What it found

• All 44 responding programs used methods capable of detecting alpha-thalassemia, and 41 (93%) reported the results.
• 25 (57%) used two screening methods, 14 (32%) only one. The two methods were isoelectric focusing and high-performance liquid chromatography, used in either order.
• The Hb Bart’s cutoffs used to classify alpha-thalassemia varied widely, as did what was reported: some programs said only that Hb Bart’s was present, some named one suspected form (such as Hb H disease), and others several.
• Reasons for not reporting elevated Hb Bart’s included lacking the right equipment, being unable to confirm or measure levels because no commercial Hb Bart’s standard exists, and the condition’s absence from the core panel.
• Most laboratories report to their newborn screening follow-up programs and to the baby’s health care provider; parents are rarely notified directly.
• 33 (80%) of the 41 reporting programs gave recommendations for retesting or follow-up — confirmatory testing, blood counts, genetic counseling or referral to a pediatric hematologist — so 20% did not.

Why standardization matters

A new Clinical and Laboratory Standards Institute guideline on newborn screening for hemoglobin disorders leaves policies to local programs but uses a 25% Hb Bart’s cutoff in its decision tree — a value many programs do not use. More consistent screening and reporting could:

• get babies with Hb H disease to a hematologist early, before complications;
• spare babies with alpha-thalassemia trait from being misdiagnosed with iron deficiency and given iron they don’t need;
• allow genetic counseling that identifies mothers at risk of a hydrops fetalis pregnancy, dangerous to both mother and fetus — increasingly important as treatments before birth improve; and
• provide the data needed to understand how common alpha-thalassemia is in the United States, a number likely to grow as more Americans have roots in Southeast Asia, China and the Middle East.

The infrastructure already exists, the authors note; what is missing is uniformity.

Sources

Based on Bender MA, Yusuf C, Davis T, et al., "Newborn Screening Practices and Alpha-Thalassemia Detection — United States, 2016," Morbidity and Mortality Weekly Report, Centers for Disease Control and Prevention; written with the Association of Public Health Laboratories and rewritten in hubnx’s own words.