A Rare Find

Kate looks the picture of health thanks to a Rady Children’s doctor, who diagnosed and treated her rare disease.

Doctor’s discovery changes little girl’s life

By Josh Baxt

This is the story of Kate Cunningham, a 4-year-old girl with a rare disease. It’s also a story about research and how it can change people’s lives.

A fraternal twin, Kate was born prematurely but seemed fine, except for an odd rash.

“We’d go out on walks and she would have a rash wherever her skin was exposed,” says Kate’s mother, Julie. Around her first birthday, Kate started getting a fever as well as the rash at the same time every day.

“I would leave for work in the morning and have a normal baby,” says Julie. “By the time I came back in the afternoon she’d be miserable: rash, fever, burning up.”

At first, doctors thought she might have allergies, eczema, sensitive skin, even dermatographia, in which faint scratches become angry welts.

The Cunningham family tried several remedies and visited all the proper specialists, but the symptoms recurred. It wasn’t until Kate was referred to Hal Hoffman, M.D., a specialist in allergy/immunology at Rady Children’s Hospital-San Diego, that her life changed for the better.

Mystery Solved

Julie still remembers that visit with Dr. Hoffman.

“He said, ‘I’m 99 percent sure this is an autoinflammatory recurrent fever disorder called CAPS. We’re going to switch her medication, and she’s going to be fine,’” says Julie.

He was right. Within 48 hours of switching medications, Kate’s symptoms virtually disappeared.

Dr. Hoffman, also a professor of pediatrics and medicine at UC San Diego, had spent a decade determining the genetic underpinnings behind CAPS, or cryopyrin-associated periodic syndromes. In 2001, years before fast genomic sequencing became available, he identified the gene responsible for Kate’s disease. About 80 percent of rare diseases are caused by faulty genes.

Dr. Hoffman says Kate has a combination of two CAPS conditions — Muckle-Wells syndrome and familial cold auto inflammatory syndrome (FCAS).

“With FCAS, patients lead somewhat normal lives but haveto limit time in the cold,” he says. Cold temperatures cause a rash, fever and joint pain. Muckle-Wells has similar symptoms, without the cold sensitivity, but can lead to kidney damage.

Kate may escape more severe consequences because she was diagnosed early.

Treatment Gap

Kate is lucky. There are about 7,000 rare diseases but only about 450 approved treatments, according to government statistics. As a result, many people with rare diseases use drugs approved for other diseases.

To help other children, Julie is involved with advocacy groups such as Global Genes and the Autoinflammatory Alliance. She hopes the government will extend gains made by the Orphan Drug Act (enacted in 1983), which gives drugmakers incentives to develop drugs targeting rare diseases. The legislation has led to improvements, but more funding for research is needed.

“You learn about rare diseases, and it’s a whole world you never knew existed,” says Julie. “My daughter is blessed to have a therapy for her disease. I want all kids to have that.”

The promise of genomics

Kate Cunningham is extremely fortunate. Her rare condition was diagnosed quickly thanks to Hal Hoffman, M.D., an expert on the disease who happens to lives in her town, and the availability of treatments.

Kate’s case is the exception, but Rady Children’s Hospital-San Diego wants to make it the rule.

Genomic research, the study of all genes and genetic information, is key to developing new treatments for rare diseases as well as cancer, autism, diabetes and other conditions.

Almost every human disease, particularly those that afflict children, has a genetic component. For most rare diseases, there is just one mutated gene. Until recently, finding that gene and other genes that cause disease has been a needle-in-a haystack scenario. The ability to rapidly sequence DNA has been a game-changer.

“With the new technology, we can know every letter of our DNA—all six billion of them — and we can know this very quickly, within hours,” says Gabriel Haddad, M.D., physician-in-chief and chief scientific officer at Rady Children’s and chair of the Department of Pediatrics at UC San Diego. “We can make major breakthroughs that will allow us to understand disease
mechanisms and be able to treat, prevent and cure diseases.”

To help make these breakthroughs for childhood diseases, Rady Children’s has established the Rady Pediatric Genomics and Systems Medicine Institute at Rady Children’s. The Institute will assemble a team of world-class scientists and clinicians who will focus on preventing, diagnosing, treating and curing childhood diseases through genomics and systems medicine research. To advance this mission, the Institute will work closely with UC San Diego and establish relationships with other institutions.

The Institute is supported by a $120 million donation from Ernest Rady and family, and an additional $40 million from the Hospital.

Originally published in U-T San Diego, October 2014