Are you a silent carrier?

I was requested by my IVF doctor to have my genetic carrier state screened. However I had some doubt whether it is necessary – when I had my first baby my OBGYN already tested me for 5-6 genetic carrier status and I was all negative. The kit the IVF clinic uses includes nearly 300 single genetic diseases but most of them have higher incidence in other ethnic groups but not mine. When I expressed disagreement that I don’t really need this “expanded carrier status” screen, she mentioned that I could have thalassemia carrier status and also I could have X-linked recessive genes so to convince me that even my husband’s genetic tests were all negative I still have to worried about whether I have X-linked recessive genes, which could be passed to male progeny only).

However thalassemia itself could have cues on your CBC and hemoglobin electrophesis results, which are routine tests for pregnancies in the US and I was screened when I had my first kid.

I checked NEJM has published a population screening study in Hong Kong:

https://www.nejm.org/doi/full/10.1056/NEJM199705013361805

“Of the 2420 students who attended the informational meetings, 1812 (75 percent) obtained parental consent and agreed to undergo screening. A total of 1800 blood samples were obtained and analyzed (12 students were absent from school on the days on which phlebotomy was scheduled).

One hundred fifty of the 1800 blood samples (8.3 percent) had microcytosis (mean corpuscular volume of less than 80 μm3). These 150 blood samples were tested for α- and β-thalassemias and iron deficiency. The α-globin genotypes of all 150 blood samples were determined both by Southern analysis and by PCR with primers specific for the (–SEA) type of α-thalassemia deletion. Mutations in the β-globin gene clusters were determined only in blood samples with hemoglobin A2 concentrations above 3.5 percent.”

The study itself did not approve that if your MCV is normal then you don’t have thalassemia genes. For this purpose, you’d have to collect a group of patients known to have thalassemia genes and test their MCVs and even if one of them have normal MCV then MCV itself can not be used as an absolute screening tool for rule out, but it is a pretty good indicator for whether you have thalassemia. See this study:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920506/

“…seven-hundred and twenty two patients presenting ten different α-thal genotypes were considered. All patients (N=722) showed reduced MCV and/or MCH values…”

  1. genetic test should be recommended according to patient’s ethnic groups
  2. genetic counseling should be conducted before ordering the genetic tests for patients to understand the risks and benefits and the necessity
  3. some genetic disease could be screened with some much simpler tests such as CBC and hemoglobin electrophoresis instead of genetic tests.

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