A 24-year-old African American woman comes to the office with her husband for prenatal counseling. She has a 3-year-old child with sickle cell anemia from a previous marriage, and the child's father died in a car accident. The patient remarried last year and is interested in having more children. She and her new husband do not have sickle cell anemia, and the patient's husband has no other children. However, the patient and her husband are worried that their future children could have sickle cell anemia. A urine pregnancy test is negative. Which of the following is the best initial test that can be offered to this couple?

Question

A 24-year-old African American woman comes to the office with her husband for prenatal counseling.  She has a 3-year-old child with sickle cell anemia from a previous marriage, and the child's father died in a car accident.  The patient remarried last year and is interested in having more children.  She and her new husband do not have sickle cell anemia, and the patient's husband has no other children.  However, the patient and her husband are worried that their future children could have sickle cell anemia.  A urine pregnancy test is negative.  Which of the following is the best initial test that can be offered to this couple?

Quizplus · Accepted Answer

11ec160b_377c_5851_9249_19f0bd25780c_MD0001_00 Sickle cell anemia is an autosomal recessive hemoglobinopathy. Affected patients must inherit 2 mutant genes for hemoglobin S (HbS), one from each parent. In order for an offspring of 2 parents without sickle cell anemia to be affected, both parents must carry the sickle cell trait. Any offspring resulting from such pairings will have a 1 in 4 chance of having sickle cell disease (SCD). This patient is a carrier of the sickle cell trait as she has a child with sickle cell anemia. Hemoglobin electrophoresis, a type of gel electrophoresis, is used to determine if the patient's new husband also has sickle cell trait. Abnormal hemoglobin (eg, HbS), moves at a slower speed than normal hemoglobin due to the replacement of glutamic acid by valine. The husband's test results combined with the maternal family history will determine the risk that future offspring will inherit sickle cell anemia. (Choice A) The chorionic villi are part of the placenta and, as such, are fetal tissue. Once fetal DNA is obtained, DNA sequencing can be performed to evaluate for sickle cell mutation. Chorionic villus sampling (CVS) can be performed at 10-14 weeks gestation. However, it is relatively invasive and carries a risk of miscarriage, spotting/bleeding, infection, and other complications. CVS is not helpful to a patient who wishes to determine her risk prior to conception. (Choice B) It is not necessary to perform maternal hemoglobin electrophoresis as it has been established from this patient's history that she has sickle cell trait. (Choice C) Northern blots use electrophoresis to separate RNA by size, followed by the application of a DNA probe to detect a specific RNA molecule. This allows for the quantification of the RNA expression of specific genes. Hemoglobin electrophoresis is a more appropriate test for SCD as it involves the separation of protein (eg, hemoglobin) rather than RNA. (Choice E) A karyotype is a visual analysis of all the chromosomes in a cell ordered by size and stained to reveal chromosomal banding. SCD results from a single nucleotide mutation, not from any abnormality in overall chromosome structure. Disorders due to chromosomal abnormalities include Klinefelter syndrome (47,XXY), Turner syndrome (45,XO) and trisomy disorders. Educational objective: Sickle cell anemia is an autosomal recessive hemoglobinopathy. In order for a child to have sickle cell disease, both parents must be carriers. Hemoglobin electrophoresis can be used to determine the carrier status of a prospective parent who has no history of sickle cell anemia. __________ References: Diagnosis of the haemoglobinopathies. (http://www.ncbi.nlm.nih.gov/pubmed/16886045) Diagnostic approach to hemoglobinopathies. (http://www.ncbi.nlm.nih.gov/pubmed/17486507)

A 24-Year-Old African American Woman Comes to the Office with Her