Medical Detectives: The Last Hope for Families Coping With Rare Diseases

All over the country, specialized strike teams of doctors are giving hope to families who are desperately searching for a diagnosis.

The medical sleuths have cracked more than a third of the 382 patient cases they're pursuing, according to a recent paper in the New England Journal of Medicine.

The specialists, scattered across 12 clinics nationwide, form the Undiagnosed Disease Network (UDN).  Since the program began in 2014 they've identified 31 previously unknown syndromes.

“It was like Sherlock Holmes," says Euan Ashley, a professor of medicine at Stanford University. "Patients would come with mystery diseases and we would try and solve them.”

Although rare diseases are individually very uncommon, collectively they're surprisingly pervasive. In fact, if grouped together into a single category, they afflict one in 20 people in the population. That's on par with diabetes, which is often described as a national epidemic.

For the people coping with mystery conditions, cracking these cases can be life-saving or life-changing. Take the perplexing case of the two Miller boys from Marin County.

Disabled Bodies, Warm Hearts

Five-year-old Chase and seven-year-old Carson have alert minds and radiant smiles but very uncooperative bodies. The blond blue-eyed brothers are not able to sit, stand, speak or feed themselves. They've spent their lives in wheelchairs.

Even though they attend a mainstream elementary school and are cognitively functioning on par with their peers, they are both still in diapers. The boys require constant care at home or attentive individual aides in the classroom.

A Four-Year Diagnostic Odyssey

Seven years ago the boys' parents, Nikki and Danny Miller, began noticing their first son wasn’t reaching milestones like rolling over or crawling. Instead, they witnessed spastic movements and tiny hands repeatedly balling into fists. Babbling never turned into words.

When Carson was about a year old he was misdiagnosed with cerebral palsy. Then when the same developmental delays emerged in their second-born, the parents started asking more questions, which led to a four-year diagnostic odyssey with countless inconclusive lab tests. One after another, specialists shrugged their shoulders.

“It’s really tough because as a parent you blame yourself," says Danny. "What did I do wrong? Is there something wrong with my genes?”

Cracking the Case

Finally, two years ago Danny applied to the Stanford UDN clinic. After reviewing the boys' medical history, researchers ordered full genome sequencing for all four family members. It was the first time every one of their 20,000 genes would be mapped. Until recently this type of extensive testing was prohibitively expensive.

“We're rapidly moving to the point where it makes more sense to go straight to the genome rather than measuring one gene, then another, then another,” says Ashley as he pulls out his laptop to point out the clue within the family’s genetics.

The screen is divided into several rows and columns with long strings of letters that code for human DNA. Ashley points to a colored section in the MECR gene.

“You can see the two boys have inherited this variant that came from their father,” says Ashley. “One letter of 6 billion can cause these incredibly devastating diseases," says Ashley.

Unfortunately, the boys also inherited a different variant from their mother in the same gene. Neither of the boys' two copies of the gene works properly, which is why Carson and Chase have a brain disease called MEPAN syndrome. The genetic mutation affects the part of the brain that controls movement. Only 13 people in the world are currently known to have it, and there is only one published scientific paper on it.

Currently, there is no treatment for MEPAN, but Danny and Nikki are hoping a heavy cocktail of vitamins and supplements will slow their boys’ brain decline. The parents also take the boys to physical, occupational and speech therapy to strengthen their muscles and teach them life skills. The boys communicate with computers attached to their wheelchairs.

Discovering what was wrong was only a single step on the family's journey, though a crucial one. A diagnosis is key to refining treatment and potentially attracting more scientific interest, which may someday lead to a cure.

The father's voice cracks as he contemplates the road ahead.

“Recently at school Carson built a sentence that said, ‘I hate my wheelchair,’” recalls Danny.  “Because I know that he wants to be up running around, playing tag, and hide and seek with the other kids. That may not be the way things work out. But I’m going to do everything in my power to try and make sure that does happen.”