The American College of Obstetricians and Gynecologists recommends that heterozygote (carrier) screening be offered to members of specific ethnic groups at increased risk for certain well-characterized autosomal recessive disorders that have available highly sensitive and specific prenatal diagnostic tests.

α-Thalassemia occurs most often in individuals of African or Asian descent. It is caused by deletion of one or more of the four α-hemoglobin genes normally present. The most severe form, deletion of all four a genes, results in fetal hydrops and stillbirth. β-Thalassemia occurs most often in individuals of Middle Eastern or Mediterranean descent. The homozygous condition (thalassemia major, Cooley’s anemia) renders an individual severely anemic in infancy. Prolongation of life requires frequent transfusions and is complicated by sequelae of iron overload.

The screening test for both types of thalassemia is the mean corpuscular volume (MCV). MCV is routinely included in an automated complete blood count (CBC). A value of 70 fL or less is a positive screening test result. Evaluation of a patient with a low MCV includes iron studies to exclude iron deficiency anemia as the etiology of low MCV, hemoglobin electrophoresis to define or exclude specific hemoglobinopathies, and paternal MCV to assess fetal risk. DNA testing on fetal cells is available for prenatal diagnosis of α- and β-thalassemias when indicated.

Sickle cell disease occurs primarily in individuals of African descent. It is characterized by a tendency of the red cells to become distorted under low oxygen tension. This causes vascular occlusion and infarction in somatic and visceral tissues, and results in painful crises. It may be fatal in early childhood. Sickle cell disease results from a single nucleotide substitution in each of the two β-hemoglobin genes. The mutation is identical in all affected individuals. The screening test for sickle cell disease carrier status is hemoglobin electrophoresis. DNA testing is available for prenatal diagnosis of sickle cell disease using fetal cells. A compound heterozygote, with a sickle hemoglobin gene and a β-thalassemia gene at the two β-hemoglobin loci, can result in a clinical picture similar to sickle cell disease.

Tay–Sachs disease occurs most frequently in individuals of Eastern European Jewish (Ashkenazi) ancestry. It has also been identified at increased frequency in a French-Canadian population. An individual homozygous for Tay–Sachs disease develops normally until the age of 6 months, then undergoes neurologic deterioration and dies in early childhood. Tay–Sachs disease results from deficiency of the enzyme hexosaminidase A. Carrier testing utilizes serum hexosaminidase A measurement. Enzyme levels are altered in pregnancy, requiring use of a leukocyte hexosaminidase measurement in the screening of pregnant patients. Prenatal diagnostic testing for Tay–Sachs disease is available for couples at risk, using a combination of DNA testing with enzyme assay in cultured fetal cells.

Cystic fibrosis (CF) is an autosomal recessive disorder. Manifestations include severe chronic lung disease with onset in early childhood, digestive enzyme deficiencies, and male infertility. The carrier rate for cystic fibrosis is increased in individuals of Northern European descent, and in those of Eastern European Jewish ancestry. Mutation detection is possible with a high rate of sensitivity and specificity in these two groups. A recent NIH consensus conference report on cystic fibrosis screening made a broad recommendation for screening for all couples planning to have children. That recommendation is not supported on a cost–benefit basis for the population as a whole. It is reasonable to offer CF testing to couples with Northern European and Ashkenazi Jewish ancestries or other couples who express the desire to be tested when they present for genetic counseling and prenatal diagnosis. Interpretation and clinical decision making are complicated for couples who have positive CF screening results, due to inexact correlation between the genotype and phenotype and the evolution of treatment for the disorder, which has led to improved health and longevity for affected individuals.