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.

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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.

  • Help!! My sister is in desperate need of an answer! She has severe inflammation and sores in her mouth. Very painful, she can’t eat, talk and is severely depressed because we can’t get any answers to what this is. She has been to several doctor’s, specialist, had biopsies done. To no prevail. We need a miracle doctor to diagnose her! Please, can someone help her!!

  • I have never contacted you before.
    What is this and why did it happen, for 14 years I have associated it with consuming wheat or wheat products.
    Sunday night February 23 a little after 11pm I started to have mild cramping in my foot. At this time I got ready and went to bed. The cramping continued and began to increase it was in my calf and increasing in pain. I got up as soon as I stood as usual I needed to void. Went back to bed very sleepy but in a lot of pain. My mind was racing it felt like “wheat” cramps but I had not eaten out and I knew everything I had eaten that day was gluten free. I got up again to try to stretch again still Very Painful. Not helping back to bed. Got up again walked to kitchen and back getting worse now in both inner thighs tried to put socks on my cold feet could only manage 1. Back to bed not for long felt the urge to defecate I hobbled to bathroom in intense pain was unable to bend to sit on toilet so I stepped toward door. Then I found myself on bathroom floor with my head between toilet and wall, in unimaginable pain both legs were shaking uncontrollably I could not bend to get up. I do not remember a fall and have no idea how long is was there. I banged on the wall but realizing I could not awaken my deaf husband I scooted on the floor to the bathroom counter with my arms and pulled my phone down and called my son sleeping in the other end of the house, it was 1:33am. He helped me up and to bed. By now the intense pain was improving and I slept. Monday was a busy day. I found myself in the bathroom often pretty sure I eliminated my entire gut over the day. By evening I could barely walk and I was very sore, I took Ibuprofen, Tylenol and Gabapentin and went to bed. The next day I felt fine no pain in my legs just soreness and a sore spot was on my shoulder that was developing a bruise.

    I have been a fibromyalgia sufferer since my 30’s I am now in my 70’s. 15 years ago I was in a crisis that I could not get out of. Constant pain was my plight my doctor sent me to 6 weeks of therapy at a pain clinic with no improvement. He then sent me to another 6 week pain therapy clinic in another town. This pain clinic doctor referred me to her father a retired anesthesiologist who had an acupuncture clinic. After 2 months with no relief he suggested I go off all grains. I immediately stopped all grains it took about a month before I started to feel better than I had felt in years. Gradually I was able to add grains without pain all except wheat. Every time I get the smallest amount of wheat I have cramping. As long as it is a small amount the cramping is not severe. The first time this bazar event happened I went to the ER they acted like I was making it up. All of my lab test were dead normal. The first event happened after 9 months of no wheat. For a special event I ate a full Italian meal and cake. I felt yucky for 8 hours of my night shift and when I lay down to sleep the bazar event happened very much like this recent event. I have searched for 14 years and can’t find anyone who has had anything similar. I think my doctors think I am exaggerating or worse making it up. I still read labels faithfully and try very hard to avoid wheat. Now I do not know what to avoid or how to keep it from reoccurring.

  • What is this and why did it happen, for 14 years I have associated it with consuming wheat or wheat products.
    Sunday night February 23 a little after 11pm I started to have mild cramping in my foot. At this time I got ready and went to bed. The cramping continued and began to increase it was in my calf and increasing in pain. I got up as soon as I stood as usual I needed to void. Went back to bed very sleepy but in a lot of pain. My mind was racing it felt like “wheat” cramps but I had not eaten out and I knew everything I had eaten that day was gluten free. I got up again to try to stretch again still Very Painful. Not helping back to bed. Got up again walked to kitchen and back getting worse now in both inner thighs tried to put socks on my cold feet could only manage 1. Back to bed not for long felt the urge to defecate I hobbled to bathroom in intense pain was unable to bend to sit on toilet so I stepped toward door. Then I found myself on bathroom floor with my head between toilet and wall, in unimaginable pain both legs were shaking uncontrollably I could not bend to get up. I do not remember a fall and have no idea how long is was there. I banged on the wall but realizing I could not awaken my deaf husband I scooted on the floor to the bathroom counter with my arms and pulled my phone down and called my son sleeping in the other end of the house, it was 1:33am. He helped me up and to bed. By now the intense pain was improving and I slept. Monday was a busy day. I found myself in the bathroom often pretty sure I eliminated my entire gut over the day. By evening I could barely walk and I was very sore, I took Ibuprofen, Tylenol and Gabapentin and went to bed. The next day I felt fine no pain in my legs just soreness and a sore spot was on my shoulder that was developing a bruise.

    I have been a fibromyalgia sufferer since my 30’s I am now in my 70’s. 15 years ago I was in a crisis that I could not get out of. Constant pain was my plight my doctor sent me to 6 weeks of therapy at a pain clinic with no improvement. He then sent me to another 6 week pain therapy clinic in another town. This pain clinic doctor referred me to her father a retired anesthesiologist who had an acupuncture clinic. After 2 months with no relief he suggested I go off all grains. I immediately stopped all grains it took about a month before I started to feel better than I had felt in years. Gradually I was able to add grains without pain all except wheat. Every time I get the smallest amount of wheat I have cramping. As long as it is a small amount the cramping is not severe. The first time this bazar event happened I went to the ER they acted like I was making it up. All of my lab test were dead normal. The first event happened after 9 months of no wheat. For a special event I ate a full Italian meal and cake. I felt yucky for 8 hours of my night shift and when I lay down to sleep the bazar event happened very much like this recent event. I have searched for 14 years and can’t find anyone who has had anything similar. I think my doctors think I am exaggerating or worse making it up. I still read labels faithfully and try very hard to avoid wheat. Now I do not know what to avoid or how to keep it from reoccurring.

  • From what you describe, it sounds as though you may have a circulation problem, especially since your lips turn colour, plus you have fatigue & shortness of breath. See you doctor!

  • For over a year now, I have been fighting massive headaches. Stabbing pain in my left chest. Fatigue, shortness of breath. Dry heaves. Pryer to this I was in the gym 6-7 days a week. Sometimes when I get real short of breath my lips turn gray!!!!! PLEASE HELP. Sincerely Mike Reeve

  • Hi the last month I have had one crazy thing after another happen. First I had lower back pain usual I have scoliosis didnt think much about it 5 days later woke up and couldn’t move my neck it was all messed up then the next day woke up tried to eat and everytime I moved my jaw my ear and temple hurt. Two day later I started having chest pain so bad I litterly called an ambulance thought I was having a stroke with the neck face arm pain then chest pain. Couple weeks go by neck back still messed up jaw on and off chest pain on and off and then out of no where my ankle starts getting shooting pain in my Achilles tendon go to er again say I have tendonitis and then as I am driving home it feels like there’s some crazy vibrating in my head. Oh and my vision has been blurry on and off too never go to the doctor I dont understand how all these things are. Happening one after another feel like my body is attacking me they said my blood work was normal ekgs normal and neck x ray normal what is wrong with me.

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