WHITTIER, Calif. — Lynn Whittaker stood in the hallway of her home looking at the framed photos on the wall. In one, her son Andrew is playing high school water polo. In another, he’s holding a trombone.

The images show no hint of his life today: the seizures that leave him temporarily paralyzed, the weakness that makes him fall over, his labored speech, his scrambled thoughts. Andrew, 28, can no longer feed himself or walk on his own. The past nine years have been a blur of doctor appointments, hospital visits, and medical tests that have failed to produce answers.

“You name it, he doesn’t have it,” his mother said.

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Andrew has never had a clear diagnosis. He and his family are in a torturous state of suspense, hanging their hopes on every new exam and evaluation.

Recently, they have sought help from the Undiagnosed Diseases Network, a federally funded coalition of universities, clinicians, hospitals, and researchers dedicated to solving the nation’s toughest medical mysteries. The doctors and scientists in the network harness advances in genetic science to identify rare, sometimes unknown, illnesses.

At the University of California, Los Angeles, one of the network’s sites, Andrew’s medical team would map his genetic makeup, then bring him in for a week of exams and consultations with specialists.

On a Monday morning in late January, Andrew and his parents were in an exam room at UCLA. Lynn teased her son, saying she was going to put him in a freezer until doctors figured out what was wrong.

“Then we’ll pull you back out again,” she said, smiling.

“I’ll never get pulled out,” Andrew responded.

“Yes, you will,” she said. “You will.”

Andrew Whittaker
Lynn Whittaker holds an old photograph of her son playing water polo.

A life-changing mystery

Andrew Whittaker’s odyssey began one afternoon at age 19, when he started trembling and couldn’t speak. Doctors suspected he was suffering from anxiety and prescribed medication to control it. But Andrew said he continued to have “episodes,” during which everything just went blank.

“It’s like there’s not enough blood going to your brain,” he said. “You can’t think.”

Andrew also started losing his balance and falling off his bicycle. The family visited several hospitals. Doctors discovered that the receptors in his brain were malfunctioning and that he lacked sufficient dopamine, a chemical compound in the body responsible for transmitting signals between nerve cells. As a result, Andrew has some symptoms similar to those of Parkinson’s disease. Doctors also confirmed he was having seizures.

Still, Andrew’s symptoms didn’t add up to any known disease.

One afternoon last fall at precisely noon, as Andrew sat propped up on the living room couch, Lynn’s phone alarm sounded, signaling it was time for his medication. Lynn pried open Andrew’s hand, which was clenched into a fist, and dropped in the pills.

To keep Andrew from falling, the family has lowered his bed and removed carpet from the house. They also bought him a wheelchair. Their precautions don’t always work. One morning, Lynn was in the kitchen when she heard a crash. “I ran in there and he’s laid flat on his back,” she said.

Andrew is close to his mom. But he also gets frustrated. He can’t shower or dress without her help. He’s had to give up the things he loved to do: printing T-shirts. Skateboarding. Shooting short films. He’s lost friends and can’t imagine dating anymore.

“Girlfriends? Forget about it,” he said, his face twitching as he talks. “They want a guy who can do stuff for them, not the other way around.”

Lynn gives Andrew his medicine. Heidi de Marco/KHN

Writing a new disease encyclopedia

The Undiagnosed Diseases Network was founded in 2015 with a $43 million grant from the National Institutes of Health. Building on work already being done at the NIH, the initiative expanded to include universities across the country: Duke, Columbia, and Stanford are among the other sites. The goals are to provide answers for patients with mysterious diseases and to learn more about the disorders.

A proposal last month by President Donald Trump to cut the NIH budget by $5.8 billion could put the program in jeopardy.

Even with the best technology and the finest brains at work, progress is slow. Since its launch, the network has received nearly 1,400 applications on behalf of patients. It has accepted 545 for review so far. Just 74 of the cases have been diagnosed, including 11 at UCLA. Andrew Whittaker’s case is among many in progress.

It’s like battling “an unknown enemy,” said Dr. Euan Ashley, one of the principal investigators of the network’s Stanford University site. “That is a particular form of torment that other patients don’t have.”

A diagnosis can end families’ painful odyssey while helping physicians and scientists better understand rare diseases and human physiology, said Rachel Ramoni, former executive director of the network, which is based at Harvard University.

Researchers throughout the network use advanced medical technology. For example, to study patients’ gene expression and disease progression, they can make models using nearly transparent zebrafish, whose genetic structure is similar to that of humans. And scientists can conduct whole genome sequencing, which allows the medical team to read a patient’s DNA and identify changes that can reveal what may be causing a disease.

“We have powerful techniques to look at every gene that is being expressed as well as every gene that is inherited,” said Dr. Stanley Nelson, one of UCLA’s principal investigators and the lead doctor on Andrew’s case. “This is an example of true precision medicine.”

Nelson said the network can examine all known genes — not just the ones believed to have mutations that cause diseases. Doing that can lead to the discovery of new illnesses.

“Part of what we have to do is keep building that library, that encyclopedia of what gene and what gene mutations cause what symptoms,” Nelson said. “It’s just incomplete at this moment.”

Already the work is helping patients and their families come to terms with their illnesses. In one case, at Stanford, a toddler was diagnosed with two rare diseases, including a connective tissue disorder called Marfan syndrome, after doctors conducted a form of sequencing that looks for changes in coded genetic segments known as exons.

Sometimes answers come from something decidedly lower-tech: collaboration among clinicians and researchers who share experiences, data, and expertise.

“A lot of times your ability to be diagnosed depends on who is in the room,” Ramoni said. “And what we are doing with the network is we are expanding exponentially the number of people in the room.”

Doctors at one institution might think their patient is a unique case, only to learn that colleagues elsewhere have a patient with a similar illness. But even when diseases are diagnosed or gene mutations are discovered, treatments may still not be available.

Dr. Stanley Nelson performs various tests on Andrew during an appointment at UCLA.

Running the medical gauntlet

Nelson, Andrew’s main doctor, walked into the UCLA exam room at the beginning of the family’s week there. He told Andrew he’d read through the medical records. “We’re going to try to figure you out.”

The work Nelson does is personal. His teenage son, Dylan, has Duchenne muscular dystrophy, a genetic disorder that causes muscle degeneration and weakness. Nelson knows his son’s disease will eventually take his life, but he said having a diagnosis makes all the difference.

“My heart very much goes out to the families that don’t even get an adequate diagnosis,” he said.

Nelson suspects that Andrew’s disease is genetic as well.

He asked the Whittakers to describe their son’s journey and he conducted a short physical exam, asking Andrew to push against his hand and touch his own nose. Andrew trembled and his shoulders tensed, but he did it.

The rest of the week, Andrew underwent several other diagnostic tests, including a muscle biopsy, an EEG, MRI, and a lumbar puncture. He remained upbeat, though running the medical gauntlet clearly wore him out. He also met with UCLA specialists in brain degeneration and muscle and nerve disorders.

At week’s end, Nelson sat down with the family to explain what he’d found. He had reviewed Andrew’s genome and compared it with that of both parents. Andrew had one copy of a defective gene that leads to Parkinson’s but the genome sequencing didn’t show a second copy, without which it could not be Parkinson’s.

He also explained that Andrew’s illness was clearly progressive and that his brain was shrinking, making it harder for him to process language and information. Nelson said he still didn’t have a diagnosis — he believed it was a brand-new disease.

Nelson planned to continue poring over the test results, conducting additional exams, and communicating with others in the network. He also is analyzing Andrew’s muscle, skin, and blood to see whether any mutated gene is expressed abnormally.

Even in the absence of a clear diagnosis, Nelson said, rare diseases like Andrew’s help educate scientists and may help other patients. “These are the people we as a society will owe a great debt of gratitude,” he said. “They are effectively donating their lives to this process.”

Lynn Whittaker was disappointed. “We are still left with just hope that they will come up with something,” she lamented. “What else do we have?”

Andrew said his relatives have asked if he’s scared the doctors will find something. “I’m more scared if they don’t,” he replied.

Kaiser Health News, a nonprofit health newsroom whose stories appear in news outlets nationwide, is an editorially independent part of the Kaiser Family Foundation.

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  • I am a veteran and was exposed to Agent Orange. I have been to every kind of doctor you can imagine. There is no help from the VA, they denied and reject any request I have. When I tell doctors I need information for the VA they run the other way. My life is worthless for I cannot do anything. I sit in my chair for hours waiting for this dyeing feeling to pass. My problem is not in the text books so doctors hear my symptoms and almost turn around and walk out. Are there doctors that can go beyond what they learned from a text book and do research for us that live in constant pain, have no quality of life and are just waiting to die??? I would love to find a doctor that can go beyond his/her text book learning and find out what is killing me. I live in Texas and have been to doctors in Houston and San Antonio. All the text book test have not shown anything conclusive to my symptoms. I am sick 24/7 and am losing hope. I have lived with PTSD for years but not acknowledge by the VA. Approximately 5 year ago my attacks(that is the way I know to refer to them) occurred every one or two weeks. Now they are every day. I am at my wits end and desperately need to find a doctor that can go beyond text book theory…….can anyone please help me or street me in the right direction???
    Dyeing to find Help.

  • I have been stricken with an diagnosed condition for about 61 years and I kept telling my doctors that I did not give a darn if I was diagnosed with something that would kill me in a day, so long as I get a real diagnosis. Still waiting. Seems an autopsy might be the only way to find out. Too bad I can’t be here then to get that elusive answer, even if they bothered to check it out.

  • I think he needs to rule out Bartonella. It could be the cause of unusual symptoms. Galaxy labs has the best test for that. Especially if he had some contact with animals.

  • “A brand new disease”. That’s scary!!! There are diseases out there which doctors know exist, but are rare., & because it’s rare, they dismiss the possibility because of the rareness. This can be a deadly attitude! My cousin’s husband died of Giant Cell Arteritis. At first he lost his eyesight., & was experiencing excruciating headaches. Opthalmolgists were fighting to save his sight, but what little sight he had left was what he had for the rest of his life. Apparently, the investigation as to why this happened to him was focused on the sight loss., then things got much worse, until finally a doctor who saw him knew what was going on. Nurses hadn’t seen it. This disease strikes approximately 10 out of 100,000 people. Rare yes., but it does happen. When it does strike, it’s those of Scandinavian descent., but who is to say this is cast in stone? In my opinion, doctors need to get rid of the attitude of “it’s so rare, you likely don’t have it”. Really??? Test for it anyway!!!!
    My cousin’s husband was rushed to hospital time after time., until he finally passed away last July. My cousin was heartbroken of course. They’d been married 52 years.

  • My brother in-law presents with uncontrolled blood sugars as well as neurological issues. He presents as a type 1 and type 2, ends up in the hospital from falls, stroke like behavior. MRI’s PET scans present as normal, but his bouts with very low blood sugar and uncontrollable highs put him in DKA or stroke. We just don’t know where to turn to, and are willing to get him to a specialty hospital or clinic that will take his erratic symptoms into other possible diagnosis. Please direct us to a source we can research and gain opportunity to get a diagnosis.

  • The story was interesting, but there was nothing to help those of us struggling with undiagnosed diseases. A contact email or anything would have meant the world to people like me, and been relevant to the article. Not sure why the author thought it was ok to get their political shots in when it had ABSOLUTELY NOTHING to do with the article either. Regardless of your political views, it takes away from the point of the piece.

    • I’m thinking that maybe Andrew’s body is either lacking certain vitamins or not processing them correctly.

  • This article was to give names of specialists for undiagnosed diseases, but I do not see one – only an article about one family with problems.

  • Oh how I know what it’s like to be feeling downright ill 3-4 days out of 7. MRI of the lumbar/cervical/brain showed some deteriorating discs, & severe narrowing of the neuro foraminal opening on one side, moderately so on the right. My shoulders are sore, & I believe the nerves are being irritated or pinched because the muscles are irritating them. The MRI results are 1 1/2 yrs old, & I’m seeing my Family Doctor in 2 weeks & will TELL him I want another MRI to see if things have worstened, which I believe they have. I also get a tight band around my head, & the headache is mostly at the back, BUT I also get a sharp pain at the top right of my head. Tension headache??..I don’t believe so..I do believe I’ve got Occipital neuralgia. I’m fed up with doctors scratching their heads not knowing what’s going on with me, so I get the label “idiopathic”. I also have a burning sensation in my feet & shins at times. My right hand will get sensations of needles, but I believe this is from the nerves being irritated in my neck. I’m totally at wit’s end with it all.
    Getting an MRI could take at least 3 months, but I’m certainly willing to wait. I need an answer..any answer. The not knowing what’s going on certainly is upsetting me.

  • I have been suffering from severe balance problems and amnesia. It occurs from my uper neck to my back that I cant move. And i forget things badly. I cant read anything or eat. I cant come up with reasoning things. My MRI and EEG is clear. My docters says that I have depression and I have been using antidepressants for a year but I am getting worse and worse day by day. Plus I didnt face any trauma in life as my psycologist say I m clear towards them. Please help me. I am dying day by day bcz of my imbalance problem and memory. I am from Pakistan. Please send me some help or otherwise I will end my life

    • See a neurologist right away. This could be one of several conditions but most are treatable. Please don’t end your life. I too am undiagnosed but I’ve been searching for a few years and I won’t stop until I find a treatment that will work with or without a diagnosis.

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