Newborn screening for non-sickling hemoglobinopathies

Abstract

The hemoglobinopathies encompass a heterogeneous group of disorders associated with mutations in both the alpha-globin and beta-globin genes. Non-sickling disorders are found primarily in individuals of Mediterranean, Asian and Southeast Asian ancestry. With rapid growth in the Asian and Hispanic segments of the US population, the geographic distribution of hemoglobinopathies is expected to become significantly different from what it is today. The epidemiologic changes in the prevalence of non-sickling hemoglobin disorders have important implications for future public health programs, including newborn screening. The purpose of newborn screening for hemoglobinopathies is to identify clinically significant disorders and provide early education and specialized care prior to the onset of clinical symptoms. Although newborn screening for sickle cell disease is mandated in all states, screening for non-sickling hemoglobinopathies is directed in only one state and limited to reporting of a presumptive diagnosis in most other states. Early delivery of comprehensive care, as well as new and potentially curative therapies, has significantly improved the prognosis for affected patients. This review will consider the increasing prevalence of once uncommon hemoglobinopathies in the US, highlighting the rationale for expanding newborn screening beyond sickle cell disorders.

Clinical Manifestations of -Thalassemia

“…Once rare in North America, it is becoming a major public health problem. There has been a 2000% increase in Asian and other at-risk populations immigrating to the United States in the last three decades (Hoppe 2009). This has resulted in California establishing universal newborn screening for a-thalassemia, and consideration of a national a-thalassemia newborn screening policy (Benz 2011).…”

“…Most of them are named by the place of origin of their discovery. The most common form is the Southeast Asian deletion ( -SEA ) (Chui and Waye 1998;Hoppe 2009). This deletion involves both a genes but not the embryonic globin genes (Chui and Waye 1998).…”

“…Hemoglobin A 2 levels are lower in a-thalassemia disorders. Automated high-performance liquid chromatography (HPLC) is an excellent screening method for high-risk populations and in newborn screening programs (Lorey et al 2001a;Hoppe 2009;Michlitsch et al 2009;Kidd et al 2010). In the neonatal period, hemoglobin Bart's is commonly seen on HPLC or hemoglobin electrophoresis.…”

Birth prevalence of disorders detectable through newborn screening by race/ethnicity

“…Only limited race-specific disorder profiles have been reported elsewhere. Previous research has examined the relationship between ethnicity and a single genetic disorder, including the prevalence of a mutation or disorder within a specific ethnic group, [4][5][6][7][8] within several ethnic groups in a region, [9][10][11][12][13][14][15][16][17] or by geographic region only. 18,19 No studies have published the disorder prevalence rates by specific racial/ethnicity groups in a large US population.…”

Implementation of Newborn Screening for Hemoglobin H Disease in Mainland China

“…High performance liquid chromatography (HPLC), however, is the traditional common technique currently employed in the majority of laboratories. HPLC is effective in neonatal screening for hemoglobinopathies [17][18][19][20]. There were studies comparing diagnostic performance between the Sebia Capillarys 2 system and HPLC, and found that both techniques were suitable for the identification and quantification of both common and unusual hemoglobin variants, producing comparable results [21,22].…”