Aware for Rare: Exploring Current Challenges in Rare Disease - PART I


In this four-part series, we examine the various challenges faced by patients and families affected by rare diseases. We also interview clinicians, researchers, and the advocacy community at large to understand their perspectives on bottlenecks in rare disease diagnosis and treatment.

Part I of the series discusses the challenges of the limited access to Next Generation Sequencing.

Mike and Joanne Nelson’s 13-year-old son, Luke, was born with profound hearing loss, hypotonia and retinal dystrophy. His doctors suspected the symptoms were a result of congenital CMV, so he was started on various therapies and started wearing cochlear implants. However, his health did not improve.

“Five years ago, after he had the cochlear implants removed, he had a nasty round of pneumonia that left him unable to walk even after he was better,” Joanne said. “Bloodwork showed elevated creatinine kinase levels, which we knew CMV had nothing to do with.”

Multiple specialist visits, biopsies, and lab tests later--all of which came back with more questions--Luke continued to deteriorate. He was completely non-ambulatory, blind, on pulmonary support, on catheterization and bowel plans, on pain medication for neuropathy, and using a G-tube for medication, hydration, and nutrition when he couldn’t eat.

In 2016, Mike and Joanne welcomed another son to their family, Clay. He had the same symptoms of his older brother Luke--hearing loss, mild hypotonia, and retinal dystrophy.

“You can imagine our fear,” Joanne said. “Now we knew this was a genetic condition. We were going to have to watch another child deteriorate and suffer with no diagnosis. We felt helpless.”

Despite the many advancements in genomics, many patients continue to remain undiagnosed, and families must face the challenges of simply not knowing.

Limited Access of Genetic Sequencing

According to Charlene York, the current Ohio State Ambassador for NORD’s Rare Action Network (RAN), which works to unite individuals affected by rare diseases so they can advocate for issues on the state and national levels, patients and families with rare diseases face a multitude of obstacles in their diagnostic journey. These include an average diagnosis time of 5 to 7 years and high cost of care and treatment.

“We were basically almost giving up hope of ever finding a diagnosis and just trying to manage symptoms,” Joanne said. “And insurance wasn’t going to pay for genome sequencing.”

The high out-of-pocket expenses related to genetic testing and evaluation is a challenge that Cincinnati Children’s Hospital clinical geneticist, Dr. Loren Peña, can attest to. She recognizes that many patients continue to be undiagnosed due to lack of access to the necessary genetic testing as a result of limited insurance coverage.

“Many insurance carriers are limiting coverage or they’re only allowing single gene testing,” Peña, who holds an MD and PhD in human genetics, said. “But now, with Next Generation Sequencing (NGS), it’s more difficult to find single gene testing. Or, the indications for treatment includes panel testing so we don’t have a way of narrowing down the testing strategy to one gene.”

This infracture, where insurance policies conflict with established standards of medical decision making and clinical care, poses significant challenges. Peña notes this is particularly true when patients have disparate symptoms, making it difficult for the geneticist to narrow down the category of disease.

“I usually try to target the testing as much as I can,” Peña said. “If one gene is appropriate, then a single gene test is what I’ll order. But for a phenotype like seizures, where there really might not be a specific gene in mind, then we might need to do a panel of genes involved in that phenotype.”

However, in some cases, Peña states that it becomes very clear early on that patients do not fit a specific diagnostic category, and whole exome or genome sequencing becomes a first line of attack rather than the last option in a pipeline that usually starts with single gene, panel, and microarray testing.

Although the costs of next generation whole exome and whole genome sequencing can be a financial burden for many patients and families, organizations like Rare Genomics (RG) are trying to assist by offering pro-bono whole genome sequencing through a partnership with Illumina to those who are eligible.

According to RG COO and VP of Patient Advocacy Romina Ortiz, the iHope program was launched to help patients who had no other way of accessing clinical whole genome sequencing (WGS).

“WGS can be expensive for families,” Ortiz said. “We wanted to lift the bottleneck by making the test free for any child that needs it. Every year, [iHope] has expanded. The number of patients helped, the number of hospitals and laboratories involved across the country have increased.”

“We are seeing more and more evidence that WGS can help kids get diagnosed quickly and in the process save money, improve care, and improve quality of life,” shared Ryan Taft, Senior Director at Illumina and chair of the iHope Network. “I have never worked on a case where providing a diagnosis didn't benefit the patient and their family. Ending the diagnostic odyssey means ending the suffering of the unknown.”

Ortiz said the iHope program is unique in that it does not require families to travel to a specific location for a consult, paperwork, or blood draw. If accepted to the program, the family is able to work directly with their home care team to coordinate clinical WGS with RG and Illumina. The application process with RG can take 1 to 2 months and the sequencing results are returned to the referring physician within 90 days of receiving the samples.

“The amazing, life changing, hope-giving Rare Genomics helped us get quad WGS with Illumina through the iHope program,” Joanne said. “Genetics diagnosed our boys with an extremely rare metabolic syndrome called Arts Syndrome. As far as we know from medical literature, we are the only known living cases.”

Read Part 2 of the series here, which discusses options if Next Generation Sequencing does not provide a diagnosis as well as the lack of effective treatments and therapies to cure rare diseases.