WEBVTT - Case #10: Chuck & Dr. Kastner 0:00:04.000 --> 0:00:07.560 I'd come home, I'd sort of have that fluish feeling, 0:00:07.880 --> 0:00:10.799 and then the next morning I'd be fine. So this 0:00:10.920 --> 0:00:14.040 developed into a pattern where I was in the living 0:00:14.120 --> 0:00:18.280 room sweating out a fever with tibuprofen, and then again 0:00:18.400 --> 0:00:19.919 the next day, you'd be fine. 0:00:20.640 --> 0:00:25.520 He started getting nodules on his body, like bumps, and 0:00:25.560 --> 0:00:28.080 he had been to so many different doctors. I just 0:00:28.120 --> 0:00:30.560 felt like they were just throwing a dart at what 0:00:30.640 --> 0:00:31.240 this could be. 0:00:32.040 --> 0:00:36.040 You couldn't imagine that anyone could be alive and have 0:00:36.080 --> 0:00:40.240 a mutation in that gene, so something obviously was wrong. 0:00:48.320 --> 0:00:51.920 How terrifying would it be to fight an unknown enemy, 0:00:52.440 --> 0:00:56.280 one you didn't recognize and didn't see coming. What if 0:00:56.320 --> 0:01:00.400 that enemy was coming from within a disease that even 0:01:00.520 --> 0:01:06.160 doctors couldn't identify. Nearly half of all Americans suffer from 0:01:06.240 --> 0:01:10.920 some chronic illness, and many struggle for an accurate diagnosis. 0:01:12.000 --> 0:01:18.720 These are their stories. A Lauren brit Pacheco and this 0:01:19.080 --> 0:01:35.919 is symptomatic. A chemist by profession, Chuck Stonner has always 0:01:36.000 --> 0:01:39.760 been a meticulous and strong figure for everyone in his life, 0:01:40.680 --> 0:01:43.600 with a straightforward sense of pride in what his faith 0:01:43.720 --> 0:01:46.600 and hard work is given him. Chuck is a through 0:01:46.600 --> 0:01:50.400 and through family man, extremely proud of his two kids 0:01:50.520 --> 0:01:52.040 and their growing lives. 0:01:52.440 --> 0:01:57.440 We have some big ones. They're now thirty and twenty seven, 0:01:58.160 --> 0:02:02.920 and we have a granddaughter. Her I just babysat Wednesday, 0:02:03.160 --> 0:02:05.600 which is quite an effort, but it was a lot 0:02:05.600 --> 0:02:10.120 of fun. It's interesting. My daughter's a physical therapist like 0:02:10.160 --> 0:02:15.280 my wife. My son's a chemist like I was. He 0:02:15.360 --> 0:02:18.320 just started working so in a process of cutting that 0:02:18.440 --> 0:02:20.320 final cord, which is quite enjoyable. 0:02:20.760 --> 0:02:24.960 He's very devoted to his family and to making sure 0:02:25.000 --> 0:02:25.880 that we all. 0:02:25.720 --> 0:02:27.160 Have good values. 0:02:27.919 --> 0:02:32.079 That's Tracy Chuck's wife. She describes him as loving, kind 0:02:32.320 --> 0:02:33.880 and her perfect partner. 0:02:34.680 --> 0:02:36.200 We've been so long together. 0:02:36.960 --> 0:02:41.560 I don't know how to be me without him. I 0:02:41.600 --> 0:02:44.360 don't know how to be just Tracy without Chuck. 0:02:47.160 --> 0:02:51.560 Busy, growing a successful career and loving family, Chuck never 0:02:51.600 --> 0:02:54.799 would have imagined that a mysterious disease would come along 0:02:54.960 --> 0:02:57.760 and threaten all of it, a journey that would have 0:02:57.880 --> 0:03:01.600 him going in and out of hospitals, even fighting to survive. 0:03:02.240 --> 0:03:04.920 He didn't realize it at the time, but in hindsight, 0:03:05.400 --> 0:03:08.679 it all started at a friendly softball game. 0:03:13.400 --> 0:03:16.560 In the spring or summer of two thousand and nine, 0:03:17.480 --> 0:03:20.240 I decided to get on a softball team with some friends, 0:03:21.040 --> 0:03:25.840 and I found myself like instantly pulling handstrings, like when 0:03:25.880 --> 0:03:28.639 I would run to first base. I had some interesting 0:03:28.720 --> 0:03:31.840 pains in my hips right around that time as well. 0:03:32.120 --> 0:03:35.160 How old were you, I'd see two thousand and nine 0:03:35.160 --> 0:03:37.120 would put me about forty. 0:03:36.800 --> 0:03:42.040 Five, So you probably initially just dismissed it as wear 0:03:42.080 --> 0:03:47.320 and tear and getting older, Yeah, I think so. That 0:03:47.440 --> 0:03:51.000 wasn't until other new symptoms started to pop up. Pulled 0:03:51.000 --> 0:03:54.160 hamstrings led to pain in this palvis right around the 0:03:54.200 --> 0:03:58.320 belt line. These pains would gradually fade, so they didn't 0:03:58.360 --> 0:04:01.960 concern him much. Things changed when he started to get 0:04:01.960 --> 0:04:03.640 fevers regularly. 0:04:04.280 --> 0:04:07.360 So during the day, I'd feel like I'm just getting sick. 0:04:07.960 --> 0:04:11.520 I'd come home, I'd sort of have that fluish feeling, 0:04:11.840 --> 0:04:14.800 and then the next morning I'd be fine. So this 0:04:14.880 --> 0:04:18.320 developed into a pattern, and it really got into daily 0:04:19.240 --> 0:04:23.440 fairly high fevers where I was in the living room 0:04:23.960 --> 0:04:27.440 sweating out a fever with ibuprofen, and then again the 0:04:27.480 --> 0:04:30.719 next day you'd be fine. Something obviously was wrong. 0:04:31.520 --> 0:04:34.320 He would fight through it, the fevers, and I could 0:04:34.320 --> 0:04:36.480 tell that it was going to be a bad day, 0:04:36.640 --> 0:04:38.440 but he would still I mean, if there was something 0:04:38.480 --> 0:04:40.760 we had to do, he would still do it. He's 0:04:40.880 --> 0:04:44.159 very methodical, and I think being a chemist help him 0:04:44.160 --> 0:04:44.480 with that. 0:04:45.160 --> 0:04:49.120 This mysterious pattern was becoming Chuck's new normal, with fevers 0:04:49.160 --> 0:04:52.120 peaking as high as one hundred and three. His primary 0:04:52.160 --> 0:04:56.279 care physician tried many different medicines without any success, the 0:04:56.360 --> 0:05:00.520 first signs of Chuck's long journey to come until Chuck 0:05:00.600 --> 0:05:03.000 was prescribed a regimen of steroids. 0:05:06.680 --> 0:05:11.520 I remember that that was just instant relief. Yeah, I 0:05:11.560 --> 0:05:13.760 felt good. I remember there were some big snowfalls that 0:05:13.800 --> 0:05:16.279 winter and I was out shoveling snow like it was nothing. 0:05:16.520 --> 0:05:19.960 So that worked, but a bunch of other medications did 0:05:20.000 --> 0:05:20.520 not work. 0:05:22.200 --> 0:05:25.360 For now, Chuck has found some relief from the daily 0:05:25.440 --> 0:05:29.200 fevers and pains, but he's no closer to understanding the 0:05:29.200 --> 0:05:32.640 bizarre set of symptoms he's been living with. Little known 0:05:32.680 --> 0:05:35.839 to Chuck, there is a doctor who will change his 0:05:35.920 --> 0:05:40.880 life forever. Doctor Daniel Kastner has been working tirelessly for 0:05:41.040 --> 0:05:44.479 years in the field of genetic research, a passion that 0:05:44.560 --> 0:05:49.600 sprouted unusually from his early studies in philosophy. Doctor Castner 0:05:49.839 --> 0:05:53.280 has become somewhat of a genetic sleuth of unknown diseases. 0:05:54.920 --> 0:05:57.920 It was a combination of being a little bit turned 0:05:57.960 --> 0:06:01.760 off by the drudge, if you will, of being in 0:06:02.080 --> 0:06:05.520 class eight hours a day, five days a week, just 0:06:05.600 --> 0:06:10.080 cramming facts into your head, versus having some exciting new 0:06:10.160 --> 0:06:13.280 things to understand and maybe even be a part of 0:06:13.360 --> 0:06:17.960 figuring out. And at that time in the early nineteen 0:06:18.040 --> 0:06:22.240 seventies was one of the most exciting times in immunology 0:06:22.480 --> 0:06:26.560 because we were just beginning to understand how immunology works. 0:06:27.200 --> 0:06:31.159 Doctor Castner is currently the head of the Inflammatory Disease 0:06:31.200 --> 0:06:36.520 Section at the National Institutes of Health or NIH, in Bethesda, Maryland, 0:06:37.000 --> 0:06:39.880 as part of the US Department of Health and Human Services. 0:06:40.200 --> 0:06:45.360 The NIH is the nation's medical research agency. Doctor Castner's 0:06:45.360 --> 0:06:48.640 time there started with his fellowship back in the seventies. 0:06:51.080 --> 0:06:55.360 Early in my fellowship at the NIH, there was a 0:06:55.400 --> 0:06:59.839 revolution that was happening in medicine, and that revolution was 0:06:59.839 --> 0:07:03.640 the Human Genome Project. And what the Human Genome Project 0:07:03.760 --> 0:07:08.559 allowed us to do was to comprehensively and in an 0:07:08.680 --> 0:07:14.160 unbiased fashion, survey the whole human genome to try to 0:07:14.200 --> 0:07:16.680 figure out what was the cause at least of a 0:07:16.720 --> 0:07:17.800 genetic disease. 0:07:18.720 --> 0:07:22.680 Being on the front lines, doctor Kastner saw the potential 0:07:22.840 --> 0:07:29.360 to revolutionize how doctors diagnose, categorize, and treat diseases. He hypothesized, 0:07:29.640 --> 0:07:32.920 if you could find common genetic variants shared among people 0:07:33.000 --> 0:07:36.080 with a certain set of symptoms, you could then create 0:07:36.160 --> 0:07:40.920 a very targeted and effective way to treat them. 0:07:41.240 --> 0:07:45.160 The first disease where I really tried to use this 0:07:45.520 --> 0:07:49.280 Human Genome Project approach in order to solve that disease 0:07:49.840 --> 0:07:53.960 is a disease called familial Mediterranean fever, and it's a 0:07:54.600 --> 0:07:59.280 relatively rare disease. It's somewhat common in Israel and Turkey 0:07:59.360 --> 0:08:04.720 and our me, but the patients are plagued with recurrent fevers. 0:08:05.120 --> 0:08:07.840 And so I had decided that I was going to 0:08:07.960 --> 0:08:10.680 use that as sort of a test case. And there 0:08:10.760 --> 0:08:13.800 were a lot of people who would say, oh, Dan, 0:08:13.920 --> 0:08:17.880 why are you wasting your time with this rare disease 0:08:18.000 --> 0:08:21.560 that's only found in certain corners of the world. 0:08:22.240 --> 0:08:27.440 The millial Mediterranean fever or FMF, was a potentially deadly 0:08:27.520 --> 0:08:31.240 disease before Castner was able to find the genetic variant 0:08:31.320 --> 0:08:35.320 responsible for causing it. Now it is more easily tested 0:08:35.360 --> 0:08:39.600 for and treated even in young children, saving countless lives. 0:08:40.080 --> 0:08:44.120 For doctor Casner personally, this entire journey of discovering new 0:08:44.160 --> 0:08:48.880 diseases and then effective treatments for them became a driving purpose. 0:08:50.160 --> 0:08:52.640 I've read some articles in which you referred to yourself 0:08:52.679 --> 0:08:55.840 at various points in times as a Don Quixote, the 0:08:56.120 --> 0:09:01.000 classic literary character prone to noble and and practical ideals. Yeah, 0:09:01.080 --> 0:09:04.600 I would think that Sherlock Holmes would be more applicable. 0:09:05.480 --> 0:09:08.959 Yeah, well, you know, I suppose that there's an element 0:09:09.080 --> 0:09:11.920 of both of those in my character. But I do 0:09:13.280 --> 0:09:17.320 like to take on something that's a bit heretical, and 0:09:17.480 --> 0:09:21.400 I love to, you know, at least sometimes show the 0:09:21.520 --> 0:09:26.040 naysayers that they're wrong, you know. And there's nothing more satisfying, 0:09:26.080 --> 0:09:29.120 at least in some cases than being able to do that. 0:09:29.240 --> 0:09:32.360 Not that there's any personal animosity or whatever, but it's 0:09:32.440 --> 0:09:33.760 just a challenge then. 0:09:34.240 --> 0:09:38.679 A challenge that would eventually intertwine Chuck's path with doctor Castner's. 0:09:39.720 --> 0:09:43.920 By now, Chuck had repeatedly gone through his doctor steroid regimen, 0:09:44.360 --> 0:09:48.240 but couldn't keep the constant fevers away. It's been two 0:09:48.320 --> 0:09:51.920 years since the fever started, and they're continuing to get worse. 0:09:54.160 --> 0:09:58.440 When do you remember having something stick out to you 0:09:58.520 --> 0:10:01.320 where you thought something is wrong here? 0:10:01.760 --> 0:10:06.120 Yeah, I mean probably after he started getting nodules on 0:10:06.240 --> 0:10:10.280 his body like bumps, and he had been to so 0:10:10.320 --> 0:10:13.160 many different doctors, and I just felt like they were 0:10:13.200 --> 0:10:15.720 just throwing a dart at what this could be and 0:10:15.760 --> 0:10:20.440 trying different medications, and I really thought, could this be cancer? 0:10:20.679 --> 0:10:24.160 Could this be you know, something you know more than 0:10:24.360 --> 0:10:26.880 just a flu? Chuck? 0:10:27.440 --> 0:10:30.160 How was this impacting your daily life at this point? 0:10:30.880 --> 0:10:33.600 Well, it was going to work saying I know I'm 0:10:33.600 --> 0:10:37.360 going to get a fever today, and then just basically 0:10:37.360 --> 0:10:39.520 sticking it out until you get home and then and 0:10:39.559 --> 0:10:42.760 then lay down and sweat it out. You know. I 0:10:42.800 --> 0:10:45.840 didn't stop working until twenty eighteen, so there was quite 0:10:45.880 --> 0:10:46.760 a bit of time in. 0:10:46.679 --> 0:10:50.840 There that must have been one really frustrating, but two 0:10:50.960 --> 0:10:56.839 really exhausting. It was it was Chuck's rheumatologists ran every 0:10:56.920 --> 0:10:59.920 test they could think of, and nothing came back pass 0:11:00.960 --> 0:11:05.000 He was then transferred to Johns Hopkins Rheumatology in hopes 0:11:05.160 --> 0:11:08.000 they would have more tools to give him answers. 0:11:10.720 --> 0:11:15.760 I didn't fit any particular float chart or perfect picture 0:11:15.840 --> 0:11:19.200 of symptoms that matched the disease. You know, I just 0:11:19.400 --> 0:11:22.880 got moved to Johns Hopkins. These guys are going to 0:11:22.880 --> 0:11:25.440 be able to tell me what's going on and figure 0:11:25.480 --> 0:11:27.920 things out. And then once you went there a few times, 0:11:27.920 --> 0:11:33.959 you realize they were as confused as the rhumatologist locally 0:11:34.200 --> 0:11:35.160 was well. 0:11:35.440 --> 0:11:39.719 So during this time period, how are your symptoms progressing 0:11:40.160 --> 0:11:41.800 and what things are getting worse? 0:11:42.600 --> 0:11:48.200 The consistent symptom has been the fevers. Other symptoms have changed. 0:11:48.600 --> 0:11:54.760 I started getting some pretty significant rashes on my body, 0:11:55.400 --> 0:11:57.839 sometimes even looking like they were going to break open 0:11:58.280 --> 0:12:00.719 and very big, and that that could have been on 0:12:00.800 --> 0:12:02.319 my face, on my ears. 0:12:02.960 --> 0:12:06.000 Was it cystic like? What did it look like? And 0:12:06.200 --> 0:12:07.000 was it painful? 0:12:07.520 --> 0:12:10.520 It was not painful, but they would get just very 0:12:10.600 --> 0:12:14.960 large red blotches and then they would sort of heal 0:12:15.080 --> 0:12:20.120 from the center out, so you'd see rings at the end. 0:12:20.720 --> 0:12:24.600 I'd get them on like my ear lobes, and once 0:12:24.720 --> 0:12:28.000 or twice on the bridge of my nose, and there 0:12:28.080 --> 0:12:31.000 was a fear that these things are going to break open. 0:12:31.720 --> 0:12:37.160 I can't imagine the anxiety of the unknown continuing for 0:12:37.160 --> 0:12:37.679 that long. 0:12:38.200 --> 0:12:40.760 Yeah, it's the balance of the anxiety of the unknown 0:12:41.120 --> 0:12:46.160 and the happiness of not being certain things. So when 0:12:46.160 --> 0:12:50.080 you're testing for certain kinds of asculitis and they're saying 0:12:50.120 --> 0:12:52.080 you don't have it, that's a good thing. So that 0:12:52.120 --> 0:12:54.400 gives you a little bit of relief and gets here 0:12:54.480 --> 0:12:56.800 with the frustration of not knowing for at least a while. 0:12:58.800 --> 0:13:01.920 The Johns Hopkins stuff are at a loss and Chuck 0:13:02.040 --> 0:13:05.160 is stuck in a vicious cycle. He has a big 0:13:05.200 --> 0:13:08.520 flare up, goes on another round of steroids. Things get 0:13:08.559 --> 0:13:12.480 normal for a little while, and so goes the cycle 0:13:12.720 --> 0:13:16.440 on and on. Though their faith is a source of hope, 0:13:16.600 --> 0:13:19.520 Chuck and Tracy are starting to become desperate for answers. 0:13:20.000 --> 0:13:23.480 Chuck is referred to another hospital, this time to take 0:13:23.520 --> 0:13:28.719 part in a study of undiagnosed fever syndromes at the NIH, 0:13:28.880 --> 0:13:33.240 where doctor Casner and other physician researchers have already been 0:13:33.280 --> 0:13:40.520 revolutionizing medicine using genomics. After he discovered the genetic variants 0:13:40.600 --> 0:13:45.640 that cause FMF, Casner continued to use genomics to pinpoint 0:13:45.679 --> 0:13:49.679 the source of other genetic diseases. The thrill of scientific 0:13:49.720 --> 0:13:53.480 discovery and seeing how that work changes people's lives kept 0:13:53.559 --> 0:13:57.600 up his determined energy. After solving several other recurrent fever 0:13:57.720 --> 0:14:03.200 syndrome mysteries. Casner has an another revolutionary idea. He proposed 0:14:03.200 --> 0:14:06.880 an entirely new way of categorizing these types of diseases. 0:14:08.360 --> 0:14:11.760 You then would later propose the idea of grouping a 0:14:11.840 --> 0:14:17.800 subset of autoimmune diseases into their own distinct group called 0:14:17.960 --> 0:14:19.960 auto inflammatory disease. 0:14:20.640 --> 0:14:24.720 Well, what was distinctive about these patients was that they 0:14:24.760 --> 0:14:30.080 had recurrent fevers, they had very very severe inflammation, but 0:14:30.280 --> 0:14:33.600 they didn't have auto antibodies, or they didn't have andigen 0:14:33.680 --> 0:14:37.080 specific T cells. It's something that you see in autoimmune diseases. 0:14:37.440 --> 0:14:40.680 And then shortly thereafter, I guess the philosopher and me 0:14:40.800 --> 0:14:43.720 coming out, we wrote a paper in which we imagined 0:14:44.200 --> 0:14:47.000 all of the diseases in the medical textbook and which 0:14:47.000 --> 0:14:50.880 of them might fall into the category of auto inflammatory 0:14:50.920 --> 0:14:55.320 disease and even categorize them. And then and this was 0:14:55.400 --> 0:14:58.800 just a real lucky time, it turned out that a 0:14:58.880 --> 0:15:02.240 year later, couple of the diseases that we had proposed 0:15:02.240 --> 0:15:05.880 that many people scoffed at, is they're just having fun 0:15:06.040 --> 0:15:09.560 or whatever with things. It turned out that those two diseases, 0:15:09.800 --> 0:15:12.720 the genetic cause of them was found, and it turned 0:15:12.720 --> 0:15:16.680 out to share a common domain and the gene with 0:15:16.760 --> 0:15:18.880 the familial Mediterranean fever gene. 0:15:21.240 --> 0:15:23.880 Grouping the diseases in this way made it possible for 0:15:24.000 --> 0:15:27.800 Cassner and his team to start assembling the bigger picture 0:15:27.880 --> 0:15:31.720 of how all these fever syndromes were connected. This made 0:15:31.800 --> 0:15:35.680 room for an entirely new way of trying out effective treatments, 0:15:36.120 --> 0:15:40.240 in particular for one very deadly disease that targeted children, 0:15:40.840 --> 0:15:41.800 and at least one. 0:15:41.680 --> 0:15:45.120 Of those diseases is a disease where kids that have 0:15:45.200 --> 0:15:49.560 it are born with fevers and rashes and inflammation of 0:15:49.600 --> 0:15:54.080 the lining around the brain. They go on to develop blindness, deafness, 0:15:54.120 --> 0:15:58.480 intellectual disability, and some of them die before reaching adulthood. 0:15:58.920 --> 0:16:02.880 Finding the genetics then allowed a biotech company to develop 0:16:02.880 --> 0:16:06.760 an inhibitor for what was triggering this deadly disease. 0:16:07.080 --> 0:16:11.080 And by giving them an inhibitor of this interluken I substance, 0:16:11.440 --> 0:16:14.640 it totally turns off the inflammation and these kids are 0:16:14.720 --> 0:16:18.080 now what we just saw one of them recently about 0:16:18.080 --> 0:16:20.760 a month ago at a meeting who's now a biochemistry 0:16:20.960 --> 0:16:22.240 graduate student. 0:16:22.360 --> 0:16:28.760 Wow Castener's unique perspective on genetic variants and the diseases 0:16:28.800 --> 0:16:32.960 they caused continued to change people's lives with every new discovery. 0:16:33.520 --> 0:16:37.600 He kept embracing different ways of approaching problems, and that 0:16:37.760 --> 0:16:40.000 made him receptive to a new way of trying to 0:16:40.040 --> 0:16:41.760 discover genetic diseases. 0:16:42.480 --> 0:16:44.800 First of all, I do have to give credit to 0:16:45.280 --> 0:16:48.880 the fellow in my lab who was really the proponent 0:16:49.120 --> 0:16:52.760 of taking this view. And so David Beck, who's the 0:16:52.840 --> 0:16:56.040 name of the fellow, just felt that we were too slow, 0:16:56.280 --> 0:17:00.200 and so he came up with this idea of genotype first. 0:17:00.720 --> 0:17:04.760 This approach started by finding a common genetic variant and 0:17:04.800 --> 0:17:09.720 then seeing what symptoms that caused, going from cause to effect. 0:17:10.480 --> 0:17:14.840 A subtle but life altering shift and perspective. But it 0:17:14.920 --> 0:17:16.800 didn't come without its challenges. 0:17:17.520 --> 0:17:19.879 It is like looking for a needle within a needle, 0:17:19.920 --> 0:17:24.560 and certainly it was a huge undertaking, no question about that. 0:17:25.240 --> 0:17:28.000 For a while we kind of wondered whether it was 0:17:28.040 --> 0:17:31.800 going to be successful. Theoretically it should work, so you know, 0:17:31.880 --> 0:17:34.880 we just have to do it until you know, finally, 0:17:35.400 --> 0:17:35.760 Is that. 0:17:35.680 --> 0:17:38.760 What kept you going, this kind of stubborn optimism. 0:17:39.880 --> 0:17:45.879 Yeah, you know, that's see the Don Quixote coming out. 0:17:46.480 --> 0:17:49.800 Doctor cassner By now had a decades long track record 0:17:50.119 --> 0:17:54.480 of methodically searching and testing for the specific gene variants 0:17:54.600 --> 0:17:59.680 causing fever syndrome. Similar to Chucks, he recategorized how doctors 0:17:59.760 --> 0:18:04.399 view auto inflammatory diseases, trusting his instincts to approach the 0:18:04.400 --> 0:18:08.240 diagnosis journey in new ways. He set up clinical research 0:18:08.280 --> 0:18:11.840 at the NIH with his learnings at the forefront. This 0:18:12.119 --> 0:18:15.960 is where he and Chuck would soon cross paths. So 0:18:16.160 --> 0:18:20.760 in twenty twelve you are linked with the National Institutes 0:18:20.800 --> 0:18:24.400 of Health and doctor Cassner, right, tell me the first 0:18:24.480 --> 0:18:27.160 time you went there and were you hopeful or were 0:18:27.160 --> 0:18:28.840 you just now what? 0:18:30.240 --> 0:18:32.720 So? I was pretty excited about that. It was that 0:18:32.960 --> 0:18:36.119 you're going to the place that knows about these fever syndromes. 0:18:36.640 --> 0:18:39.320 Doctor Casner, of course was probably the first person, or 0:18:39.320 --> 0:18:42.480 one of the first few people I met there. Although 0:18:42.720 --> 0:18:45.520 I was in the part of the tested group that 0:18:45.720 --> 0:18:48.919 did not show positive for any of those syndromes. I 0:18:48.960 --> 0:18:52.200 think it was about half that could be diagnosed and 0:18:52.720 --> 0:18:55.119 half could not, and I was in it could not. 0:18:56.119 --> 0:18:59.240 And at that time he was one of a number 0:18:59.240 --> 0:19:03.760 of patients are referred to us with unexplained fevers, and 0:19:03.840 --> 0:19:05.919 so at the time that we saw him, he was 0:19:05.960 --> 0:19:10.440 in his mid forties and had developed just seemingly out 0:19:10.440 --> 0:19:15.359 of the blue, unexplained fevers and elevations of various blood 0:19:15.400 --> 0:19:19.919 studies that indicated that there was inflammation going on in 0:19:20.000 --> 0:19:23.360 his body. But actually at that time, there weren't very 0:19:23.400 --> 0:19:26.760 many clues in terms of what was actually the basis 0:19:26.760 --> 0:19:27.960 of that inflammation. 0:19:28.600 --> 0:19:31.320 So each time you get that like hope, Oh, this 0:19:31.440 --> 0:19:35.919 doctor's going to be it, this doctor's going to be 0:19:35.960 --> 0:19:39.400 the one that's going to figure it out, and they 0:19:39.400 --> 0:19:42.480 see you a couple times and then you just know 0:19:42.680 --> 0:19:45.879 it's They didn't really have anything else to offer, you know, 0:19:46.000 --> 0:19:49.320 just try different medications, and you sort of feel like 0:19:49.440 --> 0:19:50.800 they're spinning a wheel. 0:19:51.160 --> 0:19:55.399 After six years of symptoms and countless tests, there's little 0:19:55.480 --> 0:19:59.120 left for Chuck to hold on to besides hope. And 0:19:59.200 --> 0:20:02.880 though the nia now offers him a sliver of optimism 0:20:02.880 --> 0:20:07.359 for finding answers, a terrifying flare up will test Chuck's 0:20:07.400 --> 0:20:13.639 resilience in this search and possibly cost him his life. 0:20:13.920 --> 0:20:17.000 It was a life or death concern because this thing 0:20:17.359 --> 0:20:19.240 had gone full force at the heart. 0:20:21.520 --> 0:20:25.439 We'll be right back with Symptomatic a Medical Mystery podcast. 0:20:37.840 --> 0:20:45.680 Now back to Symptomatic a Medical Mystery podcast. It's been 0:20:45.840 --> 0:20:48.920 almost a decade since Chuck first started showing symptoms of 0:20:48.960 --> 0:20:52.960 a mysterious illness that was slowly chipping away at his 0:20:53.080 --> 0:20:56.720 quality of life. It started with fevers and muscle pain 0:20:57.080 --> 0:21:00.119 and progressed to include nodules and rashes, all of for 0:21:00.160 --> 0:21:04.560 his body. Nine years of bouncing between doctors with little 0:21:04.600 --> 0:21:07.879 to know answers as to what was causing this, but 0:21:08.320 --> 0:21:10.840 Chuck was now being treated by a team at the 0:21:10.960 --> 0:21:15.520 National Institutes of Health, including doctor Castner, a self described 0:21:15.560 --> 0:21:19.200 Don Quixote figure, who gave Chuck hope he could finally 0:21:19.240 --> 0:21:23.280 get some answers as to what had been plaguing him. 0:21:23.680 --> 0:21:27.240 But even as research at the NIH forged ahead, Chuck 0:21:27.320 --> 0:21:29.240 had a flare up that would take him to the 0:21:29.240 --> 0:21:29.960 brink of death. 0:21:38.640 --> 0:21:41.080 We were in the mountains at his parents' house. 0:21:41.600 --> 0:21:45.240 We were there alone, and there was a snowstorm. 0:21:45.760 --> 0:21:47.720 He was having this pain in his abdomen. 0:21:48.359 --> 0:21:51.959 So another thing that Chuck would have as the disease 0:21:52.000 --> 0:21:56.320 progressed was bloating in his stomach, and he. 0:21:56.119 --> 0:21:58.159 Said, I think I need to go to the hospital. 0:21:58.520 --> 0:21:59.320 So we had to call. 0:21:59.240 --> 0:22:04.520 Nine one one Hello. The reception was terrible. I remember 0:22:04.800 --> 0:22:07.600 having a difficulty getting even through to nine to one 0:22:07.640 --> 0:22:13.720 one Hello, and thank god I was able to get 0:22:13.720 --> 0:22:14.760 them there. 0:22:15.400 --> 0:22:21.080 So went to the emergency room and my heart function 0:22:21.600 --> 0:22:26.520 was quite low, but not knowing what it was. You know, 0:22:26.640 --> 0:22:28.760 is this something that's going to you know, is this 0:22:28.880 --> 0:22:30.960 some kind of cancer that's going to take your life. 0:22:31.480 --> 0:22:36.000 Chuck was increasingly dependent on his steroid use, doubling his 0:22:36.160 --> 0:22:40.040 dosage just to get his fever, gut pain, and energy 0:22:40.119 --> 0:22:44.360 back to equilibrium. But Chuck knew this was not sustainable, 0:22:44.720 --> 0:22:47.960 and he soon returned to the NIH, hoping they could 0:22:48.000 --> 0:22:51.560 save him from the treatment loop. He was hopelessly stuck in. 0:22:52.280 --> 0:22:55.840 So went through the holidays just feeling bad, and then 0:22:56.080 --> 0:23:01.119 I had an appointment at NIH for a heart MRI. 0:23:02.119 --> 0:23:06.960 My heart function had just taken another nosedive, so they 0:23:07.560 --> 0:23:10.720 weren't gonna let me leave. I was admitted at that point, 0:23:11.400 --> 0:23:14.520 and that's when, you know, we knew about the my 0:23:14.760 --> 0:23:19.040 carditis and the cardio myopathy, and they really had to 0:23:19.119 --> 0:23:21.840 hit me with a couple of days of high steroids 0:23:21.880 --> 0:23:23.520 just to try to get the heart to recover. 0:23:24.040 --> 0:23:26.560 What were your fears at that time. 0:23:26.880 --> 0:23:29.960 Well, at that time, it was more I'm gonna drop 0:23:30.040 --> 0:23:32.600 over dead from a part attack. 0:23:33.400 --> 0:23:37.200 Ugh, I would just sit with cold rags on his head, 0:23:37.280 --> 0:23:39.440 just trying to say, I just want the fever to break. 0:23:39.480 --> 0:23:40.680 I just want the fever to break. 0:23:41.320 --> 0:23:43.399 I didn't want to leave a side because I didn't 0:23:43.520 --> 0:23:46.840 really I didn't want anything to happen and may not 0:23:46.920 --> 0:23:47.280 be there. 0:23:49.000 --> 0:23:51.720 This would go on for almost three weeks before the 0:23:51.760 --> 0:23:55.359 team at the NIH could finally get him stabilized and 0:23:55.440 --> 0:23:59.760 bring his heart function closer to normal levels. So on 0:24:00.080 --> 0:24:02.680 top of just the fear that you're gonna drop dead, 0:24:03.480 --> 0:24:09.000 have there been other lingering impacts of that episode. 0:24:09.640 --> 0:24:16.520 That's really when I started losing physical abilities. It just 0:24:16.520 --> 0:24:17.919 took a lot out of me. I lost a lot 0:24:17.960 --> 0:24:22.360 of muscle mass. I felt a lot weaker as far 0:24:22.400 --> 0:24:23.480 as what I could do. 0:24:24.680 --> 0:24:27.600 Just as Chuck was getting worse, Kassner and his team 0:24:27.640 --> 0:24:30.600 at the NIH finally found a clue. It seemed the 0:24:30.640 --> 0:24:32.480 pieces were starting to come together. 0:24:33.200 --> 0:24:39.560 What happened was a gradual realization. It was like peeling 0:24:39.600 --> 0:24:40.120 an onion. 0:24:40.560 --> 0:24:40.760 You know. 0:24:40.840 --> 0:24:43.920 When we first found something, this gene that had a 0:24:44.000 --> 0:24:48.679 mutation in at uba one was known to be so important. 0:24:48.920 --> 0:24:52.880 You couldn't imagine that anyone could be alive and have 0:24:52.920 --> 0:24:54.520 a mutation in that gene. 0:24:55.400 --> 0:24:59.199 The gene mutation on the X chromosome was found in 0:24:59.400 --> 0:25:02.320 three minute aged men who were part of the fever study. 0:25:03.040 --> 0:25:06.760 As the NIH team looked closer, they noticed all three 0:25:06.840 --> 0:25:10.959 men also had little bubble like structures called vacuoles in 0:25:11.000 --> 0:25:11.840 their bone marrow. 0:25:12.560 --> 0:25:17.320 We went back and looked up patients, my patients from 0:25:17.440 --> 0:25:22.119 eight years ago that had these vacuoles, and sure enough, 0:25:22.560 --> 0:25:26.439 when we did sequencing on them, they also had the 0:25:26.480 --> 0:25:31.000 same mutations in this gene. And so emerging out of 0:25:31.040 --> 0:25:35.560 the mist, you have this idea of what is this disease? 0:25:36.680 --> 0:25:40.800 These patients from the fever studies included Chuck Stoner. 0:25:41.600 --> 0:25:43.800 It almost was a shock at that point because you're 0:25:43.840 --> 0:25:45.800 not waiting every morning to get up and hear this, 0:25:46.560 --> 0:25:48.760 and then one morning it finally does happened. 0:25:49.640 --> 0:25:52.040 I'll never forget about it, you know, finding that gene 0:25:52.119 --> 0:25:54.240 and the moment that we found that gene. And so 0:25:54.880 --> 0:25:57.880