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Rare Disease Families Cope With COVID

Families that have members with rare diseases may face challenging situations during the pandemic. They’re experts in navigating complex medical situations, but they must now weigh the risks and benefits of taking a loved one with a complication from a rare disease to a hospital.

“We have experience living with uncertainty, for years or even decades. Many of us have experience with isolation, and medically fragile people have always needed to be careful of exposure to people with illnesses. And many of us haven’t been able to do things other families do,” said Albert Freedman, PhD, a clinical psychologist and caregiver for a 24-year-old son who has spinal muscular atrophy (SMA). He spoke at a webinar that the National Organization for Rare Disorders (NORD) convened March 31, “A Rare Response: Addressing the COVID 19 Pandemic.”

“When you hear hoofbeats, think horses, not zebras,” is the mantra taught to new medical students. Rare diseases are zebras – and some are unicorns.

Higher Risk of Severe COVID-19, But Not Necessarily of Infection

Each of the 7,000 or so rare diseases affects fewer than one in 200,000 people, but that adds up to 30 million individuals in the US and 30 million in Europe. One in every 15 of us has a rare disease. Many of the conditions are genetic.

In these strange times, rare disease organization websites steer families to the CDC’s “People Who Are at Higher Risk for Severe Illness” general guidance. The websites also explain how COVID-19 could play out against the backdrop of specific conditions.

For cystic fibrosis, for example, the danger of COVID-19 is obvious – CF is predominantly a disease of the lungs. For sickle cell disease, it’s the cycle of oxygen availability.

When oxygen level drops in a twist or turn of a capillary in a person who has inherited two copies of the sickle cell mutation, the hemoglobin molecules packing red blood cells morph from their globular forms into tiny curved daggers that deform the cell into a crescent shape. The sickled cells block circulation, dropping the oxygen level further. Sickling worsens as the excruciating pain of a sickle cell “crisis” unfolds.

A complication of sickle cell disease, acute chest syndrome, is where COVID-19 may come in. It unleashes cough, chest pain, fever, hypoxia (low oxygen level) and lung infiltrates that lead to pneumonia. What happens to people who develop acute chest syndrome who become infected?

Families who have members with inherited immune deficiencies are concerned too. But a recent study from the CDC may be good news. Researchers looked at 7,162 COVID-19 cases and found 2,692 had underlying conditions. The most common were diabetes, chronic lung disease, and cardiovascular disease. But only 264 people, or 3.7%, had impaired immunity.

That’s also good news for people who’ve had transplants. Bernhard Wiedermann, MD, a specialist in pediatric infectious diseases at Children’s National Hospital Rare Disease Institute, said at the webinar. He treats kids who’ve had heart or kidney transplants and take immunosuppressant drugs. “I was encouraged by the CDC report, that the immunocompromised weren’t a bigger chunk of the pie. I was expecting more.”

Heading To the Hospital – Or Not

Deciding when to go to a hospital is a tough decision for anyone these days, but especially for someone with a rare disease. Should they stay or should they go?

“Your rare disease may be the greater risk than the virus. Don’t let fear drive you to the ER, but don’t go the other way and not get treated when you need to. If you need a hospital, get seen and treated,” said Marshall Summar, MD, during the NORD webinar. He’s the director of the Rare Disease Institute at Children’s National. Dr. Wiedermann agreed, pointing out that many hospitals screen and separate patients with respiratory symptoms right away, to minimize exposure to the virus for other patients.

Think through scenarios ahead of time, both physicians advise. Which symptoms for a particular illness would justify the risk of infection from going to the emergency department? Is the regular hospital diverting non-COVID-19 patients elsewhere? How do you contact the regular care team? Plan for contacting providers, office visits, emergency visits, and hospitalization. And do whatever is possible using telemedicine.

It’s also important for rare disease families to have the treatment letters that their providers give them to avoid the nightmare scenario of trying to convince a doctor who isn’t familiar with a specific rare disorder that that’s what the patient has, Dr. Summar added.

The Status of Clinical Trials

Many rare diseases have no treatments, and so families participate in clinical trials. But just as a death in a clinical trial for gene therapy in 1999 derailed that field for months, so too has the pandemic impacted investigation of new treatments.

Families participating in clinical trials face a daunting list of issues:

  • Is it safe to go to the clinical center for evaluation or treatment, if the facility is even open?
  • Can monitoring be done by telemedicine? Can infusions or other treatments be given at home?
  • Are clinical trials understaffed because personnel have been diverted to treating COVID-19, or are sick?
  • Has the supply chain of medicines, reagents, swabs, and other essentials been interrupted?

The FDA has issued recommendations for clinical trials, including how investigators can modify protocols.

From the Families

Some of my friends in the rare disease community shared their thoughts and experiences on managing during these tough times. A big shout-out to all of them!

LUCAS   Daniel and Tina DeFabio are glad that they made the heart-wrenching decision to take out a do-not-resuscitate (DNR) order for their son, Lucas, when the boy underwent minor kidney surgery in December.

Lucas has Menkes disease, a problem in copper transport that causes deficiency of the mineral, which impairs several enzymes. Symptoms include poor growth, developmental delay, seizures, weak muscles, low body temperature, and characteristic kinky hair. Lucas, age 11, has exceeded life expectancy. The mutant gene is on the X chromosome and so Menkes mostly affects boys.

Lucas has Menkes disease.

In early March, Lucas’s kidney symptoms returned, and doctors told the anxious parents that a simple stent surgery could forestall kidney failure. But a simple procedure in the face of COVID-19 isn’t so simple.

In mid-March, the state that the family resides in went on lockdown. “We sheltered at home, questioning if going to the medical center was wise. Recovery time from a day of surgery could mean several days in a hospital risking exposure, and boys with Menkes disease most often die from pneumonia,” Daniel said. Hospitalization wouldn’t be safe.

The parents thought back to their DNR decision. “We are in no way cavalier, but his mom and I went into this COVID-19 scare reconciled to the strong likelihood that should Lucas need a ventilator, he might not be able to get one and we should probably decide that one not be used if available. In light of how COVID-19 could change and complicate things, we were glad to not only have the DNR in place, but to have made the decision with less panic,” Daniel said.

The family is doing well, Daniel reports, and the amazing home health care nurse left her family to care for Lucas all this time. Read Daniel’s excellent “We’re All Rare Disease Families Now” here.

ELIZA     The O’Neills are quarantine experts – they kept Eliza at home for 722 days before her gene therapy in 2016 for Sanfilippo syndrome type A (see opening photo). If the little girl became infected with the type of virus used to deliver the gene therapy, she might have mounted an immune response against the treatment. (See Eliza Gets Her Gene Therapy)

Eliza’s mom Cara Parsons O’Neill, MD, hardly expected to be back in quarantine, let alone with the rest of the country. “I’m finding it just as challenging now, though in somewhat different ways, to fill the time for Eliza. I think it’s that way for many families, but for those who have children with significant neurocognitive-behavioral-developmental disabilities, this is so very amplified.”

Dr. Parsons O’Neill worries about Eliza’s skills regressing because she isn’t getting her accustomed structure, instruction, and therapies. “Typical kids may do fine with this school hiatus, but children with special needs are generally not going to be able to have their needs met ‘virtually.’“


JACOB     Orah Melnick Lasko agrees with Dr. Parsons O’Neill about the effect of discontinued therapies. Her son Jacob has an extremely rare “USP7-related disease” (see When a Rare Mutation Causes a Rare Disease: Jacob’s Story). His condition doesn’t yet have a protein or gene therapy, and so standard approaches are important in managing common symptoms – developmental delay, low muscle tone, feeding difficulties, and abnormal gait.

“The hardest part is that all his therapies were stopped. We were going to try teletherapy for physical therapy, which was too hard given his older sisters’ school schedule. His occupational therapist sent us great activities to do,” Orah said. She’s providing his speech therapy because she did graduate work in the field. “We’re making good progress!”

HANNAH     Like Eliza, Hannah Sames had gene therapy in the summer of 2016, for giant axonal neuropathy. My book on gene therapy chronicles her family’s years-long effort.

Today Hannah, 16, works hard to build and maintain her strength and flexibility – and is vulnerable due to taking immunosuppressant drugs.

Early in the pandemic, her sister Madison returned from a semester abroad and the family went into quarantine. They took to social media to urge people to follow quarantine and social distancing recommendations to protect those with rare diseases. (See After Gene Therapy: Hannah’s Journey Continues).

TALIA Talia Duff has a rare form of Charcot-Marie-Tooth disease (CMT4J), which is similar to ALS and SMA. Like cystic fibrosis and sickle cell disease, Talia’s condition damages the organ system most vulnerable to the novel coronavirus.

“Tal has little strength left in her supporting respiratory muscles that help us inhale, exhale, and cough–intercostal muscles, chest wall muscles, abdominal muscles, the diaphragm. She hasn’t been able to cough for a few years,” explained her mom Jocelyn (see Rare Disease Day 2017: Talia’s Story).

A “cough-assist” machine had helped Talia breathe for years, but she recently moved to a sip-vent, which provides extra breaths, and sometimes uses a bipap machine. Scheduled scoliosis surgery to improve Talia’s breathing is on hold.

The family manages Talia’s respiratory decline via telemedicine visits, phone calls, and emailing with her respiratory team at Boston Children’s – a city that’s still a hot zone. So they have been self-quarantining at home, “to create a bubble around Talia. Given her respiratory status, it is unlikely she would survive COVID-19,” Jocelyn said.

The stress is mounting. “In addition to homeschooling her since schools shut down, like many other rare disease parents, the responsibility for all of her therapies rests on me. We have no one coming into our house to help, as we try to keep the virus away from Talia,” Jocelyn said. Still, she has a bag packed, ready to go, in case Talia needs hospital care.

Talia with Coco

A Final Word

Albert Freedman, the clinical psychologist whose son has SMA, said, “We in the rare disease community are experts at facing challenges and adversity. We know how to adapt. We are resourceful and creative and resilient and we know how to face complicated challenges. Those experiences will serve us well as we move through this difficult period. We can be a model for others for what it means to face adversity with great grace and dignity.”

My thanks to all of my dear friends who shared their stories.











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