For two years, Elizabeth and Michael* lived with their daughter’s diagnosis of Gaucher disease, a genetic disorder that impacts many of the body’s organs and tissues. They anxiously watched Sophie’s development through infancy into toddlerhood for early signs and symptoms. They engaged with disease advocacy organizations and patient communities, found specialists they trusted, and prepared as best they could for the financial crush of biweekly intravenous infusions that Sophie would eventually need to cope with her illness.
However, Sophie never had Gaucher disease. Her diagnosis was the result of a false positive on a lab test, caused by a nonfunctional piece of DNA called a pseudogene.
Uncovering the unexpected
When Elizabeth was pregnant with Sophie, she found out through a targeted carrier screen for people of Ashkenazi Jewish descent that she was a carrier of a relatively mild version of Gaucher disease. Carriers themselves are unaffected; it’s only when someone inherits the disease-causing variant from both parents that he or she will develop the disease. Gaucher disease affects the spleen, liver, and bone marrow and is a variable onset disease, which means symptoms may appear anytime during childhood or even early adulthood. While treatable, treatment for most people means intravenous infusions every two weeks for life. On top of the emotional and physical stress of this disease, treatment is very expensive, running into hundreds of thousands of dollars per year for a single patient – a heavy financial burden that many people cannot afford.
As Gaucher disease is most commonly associated with Jewish ancestry and Michael is not Jewish, they were advised that the chance of him also being a carrier was extremely low and he did not need to be screened.
It was not until after Sophie was born that it was suggested, by her pediatrician, that Michael should also get tested. He did and his results stated that he was a carrier of a far more severe type of Gaucher disease.
“We were shocked and scared,” Elizabeth remembers. Based on those results, their daughter suddenly had a 25% chance of developing this disease. They immediately had Sophie tested, and while enzyme function tests were in the low-normal range, which is indicative of carrier status, genetic testing indicated that Sophie had apparently inherited Gaucher disease-causing mutations from both her parents.
“We had this perfectly healthy baby girl, but this feeling of impending doom that she was going to become sick,” Michael says. They worked with specialists and established regular visits for screening tests to spot signs that the disease was manifesting.
A new lease on life
Eventually, Elizabeth and Michael decided they wanted to grow their family and have another baby. After exploring their options, they decided that pursuing in vitro fertilization (IVF) with pre-implantation genetic diagnosis would be the safest way to make sure their next child wouldn’t have the same disease. As part of that process, the couple opted to do an expanded carrier screen, this time using Sema4 to generate results for both parents.
Unexpectedly, the Sema4 results showed that while Elizabeth was a carrier, Michael was not. The couple worked closely with Lama Elkhoury, Director of Genetic Counseling Services at Sema4, to get to the bottom of these discrepant results. Extensive follow-up testing in the Sema4 labs, this time for all three family members, determined that the variant shared by Michael and Sophie was not located in the gene responsible for Gaucher disease.
Instead, it was in a hybrid copy of a pseudogene, a non-functioning gene that has remarkably similar DNA; when lab tests are less precise, it’s all too easy for them to mistake pseudogenes for closely-related disease-causing genes. Sema4 deploys multiple advanced technologies to ensure the most accurate and reliable results for all of its genetic tests. Third-party testing at another lab ultimately confirmed Sema4’s findings.
As a full-service laboratory with deep roots in academia, Sema4 was also able to repeat Sophie’s enzyme analysis in-house. Once again, her levels were in the range expected for a carrier – and this time the genetic testing results matched up. Sema4 had demonstrated that Michael was never a carrier, and that Sophie herself only had the variant from Elizabeth. Like her mother, she will live out her life as a carrier unaffected by the disease.
“We were so relieved. Sema4 really went above and beyond in terms of investigating this and tracking down the truth,” Michael says.
Following the results of their expanded carrier screen, the couple decided to forego IVF and conceive their child naturally. Soon after, Elizabeth gave birth to a healthy baby boy.
“We wanted to share our story in the hope that it might help other families who may be living with false positive results from older, less accurate genetic tests. We are so grateful to Sema4,” Elizabeth added.
*Per the family’s request, we have changed their names to protect their identity.
For more information on Sema4’s Expanded Carrier Screen solution, learn more here.