Newborn screening for hemoglobinopathies in California

Abstract

Background Newborn screening (NBS) for hemoglobinopathies facilitates early identification of affected individuals to ensure the prompt institution of comprehensive medical care for affected newborns in California. When linked to extensive follow-up and education, NBS has been shown to significantly reduce mortality in children with sickle cell disease. Due to changing immigration patterns from Asia and Latin America, the State of California has witnessed an increased prevalence of clinically significant hemoglobin (Hb) disorders, including those resulting from novel genotypes. In 1999, newborn screening for Hb H disorders was incorporated in the statewide hemoglobinopathy screening program. Procedure Primary screening for hemoglobin variants was performed using high performance liquid chromatography. Confirmatory testing on hemoglobinopathy mutations was performed by electropheresis techniques and genotyping methods. Results Of 530,000 newborn samples screened annually in California, 2,118 samples were referred to the Hemoglobin Reference Laboratory (HRL) for confirmatory testing between January 1, 1998 and June 30, 2006 (0.05%). Sickle cell disease was most frequently observed (1 in 6,600 births) followed by α-thalassemia (1 in 9,000 births) and β-thalassemia disease (1 in 55,000 births). The confirmatory analysis modified the initial screening in 5% of cases and revealed 25 rare or new genotypes. Diverse ethnicities were associated with hemoglobin mutations including Southeast Asian, Black, Indian/Asian, Middle Eastern, and Hispanic. Conclusions The California hemoglobinopathy screening program provides accurate diagnosis of hemoglobinopathies. Increasing incidence of diverse mutations require new strategies of laboratory screening, counseling, and patient management.

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

“…Newborns with initial screen-positive results were referred to a state-contracted specialty follow-up center for endocrine, metabolic, hemoglobin, 12 or CF disorders. Center specialists determined whether referred children had a disorder through appropriate confirmatory testing.…”

“…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.…”

Newborn screening for non-sickling hemoglobinopathies

“…18 The carrier frequency of the Hb E mutation among California Asians is almost equal to that of the Hb S mutation among African-Americans. 19 In California, 25% and 11% of infants born to parents of Cambodian and Thai/Laotian descent, respectively, are Hb E carriers. Hb H disease, a clinically significant form of α thalassemia, is now the second most common hemoglobinopathy observed in California and has justified universal newborn screening for this condition.…”

Non-transfusion-dependent thalassemias

“…Increasing incidences of these disorders in other areas of the world, such as North Europe and North America, previously relatively unaffected by these conditions, have also been reported. [3][4][5] The aims of this review are 3-fold. First, to highlight those genetic and environmental factors that explain the milder disease form in NTDT compared with transfusion-dependent patients.…”