DDx

Giving New Life Through X-linked Hypophosphatemia Research May 29, 2024

After a lifetime of treating her rare bone disease, X-linked hypophosphatemia, a patient is at the end of her rope. Due to a genetic variation of the X chromosome — specifically the PHEX gene — there’s an imbalance of phosphate levels in her body. Because of its domino effect on bone development and mineralization, the patient is in pain, she’s frustrated, and nothing seems to help. So when a clinical trial opportunity presents itself, Dr. Suzanne Jan de Beur, a professor of medicine and the Chief of Endocrinology and Metabolism at the University of Virginia, is unsure the patient will want to participate. While the decision to participate is surprising, the results of the clinical trial are astonishing.

The Bumpy Road to Hypoparathyroidism Diagnosis and Treatment May 22, 2024

It’s a summer day and a 45-year-old is out for a drive. As she accelerates her stick-shift car, she starts to experience familiar, and scary, symptoms: facial tingling, numbness around her mouth, and a sharp pain in her hands. Her hands cramp and lock onto the steering wheel. Fortunately, she makes it home safely, but it will take many wrong turns and the help of Dr. Google to determine a diagnosis of hypoparathyroidism, a rare bone disorder. Dr. Michael Mannstadt, the Chief of the Endocrine Unit at Massachusetts General Hospital and Associate Professor in Medicine at the Harvard Medical School in Boston, shares this patient’s story and how a clinical trial changed this patient’s life.

Unexpected Therapies for Fibrodysplasia Ossificans Progressiva Offer New Hope May 15, 2024

A local pool in the summer is teeming with kids. A 9-year-old does a cannonball into the shallow end. As she surfaces, a stab of pain shoots through her hip. As days pass, what seems like a straightforward bump takes a complicated turn. Dr. Edward Hsiao, an endocrinologist and Director of the UCSF Metabolic Bone Clinic at the University of California, describes how after discovering a new bone growth at the site of the pain and several rounds of major (and unsuccessful) interventions, the child is diagnosed with fibrodysplasia ossificans progressiva. This extremely rare bone disorder has a devastating impact on a patient’s life. But thanks to unexpected areas of research, patients have new reasons to hope.

Overcoming the Odds of Prenatal Hypophosphatasia May 08, 2024

In an examination room, an ultrasound technician moves a wand over a patient’s belly. The patient is 20 weeks pregnant. Usually, these appointments bring good news, but the news this day is devastating: the baby’s bones are broken and bowed. Despite this, the baby is born and does well. After testing, all signs point to hypophosphatasia for Dr. Eric Rush, a clinical geneticist at Children’s Mercy Hospital and the University of Kansas Medical Center, and an Associate Professor of Pediatrics at the University of Missouri-Kansas City, who shares this patient’s story. And thanks to the life-changing treatment of enzyme replacement therapy, today, this child and many others with this rare bone disease are living happy, healthy lives.

The Power and Potential of GACI Clinical Trials May 01, 2024

In a bustling maternity ward, an infant has a case of newborn hiccups. But this quickly transforms into labored breathing. A chest X-ray unravels an unexpected discovery – calcium deposits around her shoulder. Follow-up tests paint a complex picture, revealing narrowed blood vessels and widespread calcifications. Genetic testing confirms a grim diagnosis: generalized arterial calcification of infancy, or GACI, a rare genetic condition with a challenging prognosis. Nearly half of infants don't survive beyond six months. But as Dr. David Weber, a pediatric endocrinologist and the Medical Director for the Center for Bone Health at the Children's Hospital of Philadelphia, shares, a revolutionary clinical trial could potentially transform this child's life and the lives of others with this disease.

Biosimilars and the Quiet Revolution in Medicine Apr 24, 2024

On a December morning, a 62-year-old goes for a walk. There’s snow on the ground and she loses her balance. She falls and fractures her wrist. This simple fracture reveals underlying osteoporosis, requiring lifelong (and expensive) medication. But as you’ll learn from Dr. Richard Eastell, an endocrinologist and professor of Bone Metabolism at the University of Sheffield, this is where biosimilars come in. Biosimilars are extremely similar — hence the name — to the original biological drug they're designed to imitate. The excitement around biosimilars is that they’re cheaper, making them more accessible to more people, meaning fewer fractures … better health … a better economy … and ultimately, a better quality of life.

How One Child Overcame Hemophilia Complications Despite Incredible Barriers Apr 17, 2024

A 5-year-old child and his parents boarded a plane heading for a new life. They were Syrian refugees, who fled conflict in their country and then lived a difficult life in a refugee camp. Now they were heading to Canada. But soon after arriving, there’s a problem. The child has hemophilia and due to hemophilia complications, a minor injury while traveling became a major concern. Add to this a language barrier and trying to understand a new culture. Dr. Robert Klaassen, a pediatric hematologist and lead of the Comprehensive Hemophilia Care Clinic at Children's Hospital of Eastern Ontario in Ottawa, Canada, shares his experience working with a family who overcame incredible barriers and the lessons learned along the way.

Unraveling How a Hemophilia Diagnosis Went Undetected for 60 Years Apr 10, 2024

It was supposed to be a simple, low-risk procedure, but for this 61-year-old patient with undiagnosed hemophilia, undergoing a lithotripsy for kidney stones proved to be anything but. The patient was born in the 1950s in Taiwan, when many people in the country had never heard of the disease. So, despite signs throughout his life, the patient’s hemophilia diagnosis evaded him for decades. Dr. Yeu-Chin Chen, a hematologist at the Tri Service General Hospital's Hemophilia Care and Research Center in Taipei, Taiwan, shares this patient’s journey and how doctors should be on the lookout for signs of hemophilia, while understanding that symptoms can vary from patient to patient.

To Play or Not to Play, the Challenges of Managing Pediatric Hemophilia Apr 03, 2024

A young child living with severe hemophilia is adopted by a family in the United States. Prior to his adoption, due to a lack of resources and other challenges, his hemophilia was not properly managed. Dr. Meera Chitlur, a pediatric hematologist and the director of the Hemophilia Treatment Center at the Children's Hospital of Michigan in Detroit, has treated this patient since he first came to the U.S. As he grew older, like many children, he wanted to play sports. But for people with hemophilia, participating in sports brings great risk. Dr. Chitlur shares how together with the patient and his family, they navigated the challenges of growing up with hemophilia and how new treatment options for pediatric hemophilia have opened up a whole new world for kids living with the disease.

The History of Hemophilia and Its Evolution Toward Preventive Care Mar 27, 2024

About 40 years ago a mother brought her 6-month-old child into the hospital. He was covered in bruises. Dr. Victor Blanchette, a pediatric hematologist at the Hospital for Sick Children in Toronto, Canada, met the patient that day and, following a severe hemophilia diagnosis, has treated the patient ever since. Dr. Blanchette recounts how during the patient’s childhood in the 80s, the approach to treating hemophilia was reactive, not proactive. This meant that normal childhood activities could lead to devastating bleeds. During this episode, we walk through the history of hemophilia and how its evolution toward preventive care has had an incredible impact on this patient and so many others.

Undoing the Long-Held Misunderstandings of Hemophilia in Women Mar 20, 2024

A 30-year-old was in labor with her first child. Everything was going to plan … until it wasn’t. Dr. Azusa Nagao, a hematologist at Ogikubo Hospital in Tokyo, Japan, shares a case that illustrates how historically it was thought that women and people assigned female at birth could only be carriers of the disease, not have the disease themselves. This misunderstanding of hemophilia in women has led to women going undiagnosed and untreated with severe repercussions. For the patient in this story, it meant a frightening and dangerous birth experience that put her and her child at risk. Dr. Nagao also outlines efforts to educate patients and physicians about hemophilia, what to look for, and how to treat it.

The Ups and Downs of Hemophilia Treatment Mar 13, 2024

A patient was experiencing severe knee pain. Unfortunately, this wasn't anything new. For decades, he’d been suffering from joint disease, caused by severe bleeding in his knees from a rare blood disorder — hemophilia A. The patient was born in the 1960s, a time when the life expectancy for patients with hemophilia was only 10 years. But as Dr. Annette Von Drygalski, a board certified hematologist and the director of the Hemophilia and Thrombosis Treatment Centre at the University of California, San Diego, explains, advances in hemophilia treatment throughout this patient’s life allowed him — and many others like him — to live a longer, richer life.

Go Inside the Minds of Doctors Who Specialize in Hemophilia Mar 08, 2024

Go inside the minds of doctors who specialize in hemophilia — a rare, inherited bleeding disorder that once meant possibly not surviving past the age of 20. This season, we’ll explore the medical milestones that enable patients today to live longer, richer lives and examine the challenges yet to be tackled.

When the Doctor is the Bully Nov 22, 2023

What can you do when your attending physician is a bully?

Hear from two nurses, Melissa and Laura, about their experiences being bullied by a physician.

For Melissa, it was notifying an on-call physician that a baby was ready to be delivered, only to be scolded for calling too soon.

For Laura, it was being reprimanded by a physician who questioned her abilities as a nurse in front of a patient.

So how do you respond to a bully, especially when the bully is in a position of power?

Connie spoke with Carolyn Smith, an associate professor and associate dean of research, and author of "Standing Up Against Workplace Bullying Behavior: Recommendations From Newly Licensed Nurses" for insight.

Carolyn, Melissa, and Laura all weigh in on standing up for yourself, calling out bullying, and sticking to your boundaries.

Critical Learning on the Job Nov 15, 2023

When is it okay to admit that you don’t know how to do something?

Hear the story of Tamara Kuhn, a bedside telemetry nurse, who in a moment of crisis, used her problem-solving skills to keep her patient (and herself) safe.

Tamara was caring for a patient who suddenly became violent. After calling for help, Tamara was given what she thought would be a standard restraint system. But what she received was not equipment she was used to.

So how do you set yourself up for success in these situations?

Connie spoke with Jill Clemmons, an acute care nurse practitioner, for insight.

Jill discusses how taking care of yourself, preparation, and finding your why are key to navigating difficult situations.

Trusting Your Gut Nov 08, 2023

What do you do when you know something is wrong with a patient, but don’t have the data to back it up?

Hear the story of Diana Struthers Stanton, who, at the beginning of her 46 years in nursing, cared for a 10-year-old patient with Reye syndrome. The patient’s capillary refill had changed and was slowly getting worse and worse.

Concerned, Diana spoke to her charge nurse and was told not to worry about it.
She spoke with her colleagues who also told her not to worry.
She paged the on-call resident in the middle of the night, but got the same response.

Diana’s gut was telling her something was wrong, but she lacked the clinical data to back it up.

So what do you do?

For insight, Connie spoke with Dr. Sarah Kim, a specialist in emotion-focused mindful psychotherapy, about the importance of trusting your gut.

We’ll also discuss being your patient’s advocate and learning to forgive yourself when things don’t end well despite all your efforts.

When Generic Symptoms Turn Serious Nov 01, 2023

How do you know when generic symptoms are masquerading as something serious?

Hear the story of Molly Lalonde, a pediatric nurse practitioner, who met an 11-year-old patient with an unexpected concern.
While surprised by the patient’s inquiry, Molly took the time to listen and ask questions. In response to the patient’s heightened level of concern, Molly investigated further. Following an assessment by a specialist, it turned out the patient’s concern was warranted.

So how do you recognize the zebra in a herd of horses?

To get another perspective, our host Connie Levie spoke with Dr. Raj Bhardwaj, an urgent care physician and host of the DDx podcast.

Dr. Bhardwaj details how to zoom out and get the bigger picture, the importance of respecting the concerns of your patients (just as Molly did), and following your spidey sense.

Raj recommends our new show: They Don't Teach That In Nursing School Oct 25, 2023

While nursing school equips you with valuable knowledge and skills, it doesn't prepare you for the real-life challenges you’ll face on the floor.

They Don't Teach That In Nursing School is your go-to guide, offering unique solutions to the unexpected problems you'll encounter as a nurse.

Each week Connie Levie (RN) presents the story of a nurse facing a specific challenge and its possible solutions.

Our episodes are snack-sized, designed for your commute, break time, or just when you need to decompress and connect to a larger community of nurses.

This podcast is a must-listen for nursing students, recent graduates, and seasoned professionals alike, who want a deeper understanding of the profession.

Whether you're mastering a new skill, managing difficult bosses, or thriving in your nursing career, we've got you covered with practical advice and eye-opening stories from the field.

They Don't Teach That In Nursing School is a limited (four episode) series that launches on Nov 1st! Give it a listen!

RAJ WANTS YOUR VOTE Sep 21, 2023

DDx has been nominated for three Signal Awards. Click the links below and vote for us now!
Documentary: https://vote.signalaward.com/PublicVoting#/2023/shows/general/documentary
Health & Wellness: https://vote.signalaward.com/PublicVoting#/2023/shows/general/health-wellness
Best Writing: https://vote.signalaward.com/PublicVoting#/2023/shows/craft/best-writing

SPECIAL ANNOUNCEMENT FROM RAJ Sep 06, 2023

Hi DDx listeners!

We’ve got something special in the works, and we want you in on it.

We're developing a new podcast by and for nurses - and we're searching for a host!

It’s a show about innovative solutions to the most intense challenges - whether clinical or personal - that nurses face.

In each episode, you, our host, will connect with fellow nurses who are grappling with specific challenges and unravel solutions that not only elevate their practice but also enhance their overall job satisfaction.

Whether you're fresh to the nursing world or a seasoned pro, your voice matters.

We're building a community of curious minds, a place where your insights and wisdom can light the way for others.

This is a paid - not volunteer - opportunity.

So, if you're ready to embark on a journey of camaraderie, inspiration, and learning, go to https://bit.ly/NursingPodcastHost

Oh and keep in mind, our submissions will close on Sept 18 - so press that record button soon!

Thanks!

Hypoplastic Left Heart Syndrome and a Trip Across State Lines Feb 01, 2023

Following a normal first trimester, a pregnant patient starts spotting. The patient’s care provider books an urgent ultrasound to see what is causing the bleeding. The main concerns are if the spotting is caused by a miscarriage or something else.

Following the ultrasound, the technician calls in obstetrician Dr. Ashley Brant to review the results with the patient. There is a problem with the fetus’ heart — specifically, a condition called hypoplastic left heart syndrome. Essentially, the left side of the heart doesn’t develop normally and can’t pump blood in the way that it should.

Hypoplastic left heart syndrome causes poor oxygenation, meaning the skin can be bluish or with dark discolorations. It also causes difficulty breathing, feeding, and lethargy. Treatment includes multiple surgeries after birth, and can even require a heart transplant.

Without treatment, the condition is fatal.

The patient is offered genetic testing to determine if the heart condition is a symptom of a larger genetic disease. Regardless, the prognosis is grim.

The patient meets with Dr. Brant to discuss all of the options, including continuing or ending the pregnancy.

“I think everybody who's in a situation where they're thinking about ending a pregnancy because of a major fetal anomaly, they are thinking about what is the kindest decision, the most loving decision that they can make for their baby,” shared Dr. Brant. “Nobody wants to be in this position. And they're thinking about what the experience is going to be like for this child.”

The patient makes the decision to end the pregnancy through the dilation and evacuation method.

However, the procedure cannot be performed in the state because of a heartbeat law in place at the time.

And so Dr. Brant refers the patient to an out-of-state clinic where the initial procedure to stop the heartbeat can be performed. But, in order to be where the patient has the support of the medical team she knows and who has been by her side, the patient returns to her home state for the final procedure.

“No one ever envisions themselves needing an abortion. No one ever thinks, ‘I want to have an abortion,’ before they're in a position of needing one. I would just encourage compassion and empathy and trying to understand the life that someone else might be walking in.”

Pregnancy Reduction in a Twin Pregnancy Jan 25, 2023

A 35-year-old with several children discovers she is having a twin pregnancy. This is happy news, until a potential abnormality in twin B is found.

Twin B is measuring much smaller than twin A — almost a full 10 to 14 days behind — and there is fluid around the fetus. While it is too early to diagnose, it appears there is a brain abnormality.

The patient, with a lot of apprehension and many questions, sees high-risk obstetrician Dr. Maeve Hopkins. Genetic testing is needed for decision-making — to help determine if twin B can survive or if the patient’s life and twin A are at risk, meaning a pregnancy reduction will need to be considered. Dr. Hopkins orders a biopsy of twin B’s placenta.

The results from genetic testing reveal that twin B has three sets of chromosomes, instead of two. This results in a rare genetic condition that causes severe birth defects. Most pregnancies in this situation end in either miscarriage or stillbirth. While there are very rare cases of live births, survival is generally limited to an average of five to seven days.

Carrying the fetus poses significant risk to both the patient and twin A. There could be a build up of amniotic fluid and difficulty swallowing for twin B, which could lead to preterm labor symptoms and birth, as well as stillbirth. Losing twin B in utero may increase the risk of losing twin A and put the patient at risk, too.

In this case, there are two options.

One is expectant management, which is essentially to wait and see. The other is a multi-fetal pregnancy reduction, where the cardiac activity of twin B is stopped, and the patient continues with a single twin pregnancy. While pregnancy reduction is considered a fairly safe procedure, there is a small risk that the patient could still lose twin A.

“I think she was somewhat in shock,” Dr. Hopkins shared. “And I think she wanted some guidance, which is always difficult when patients want to know what to do … it's a very personal, very familial decision for the patient … I generally say these are the risks to you, these are the possible outcomes, and these are the risks of a procedure. And a procedure likely carries less risk than continuing a twin pregnancy. And ultimately, she was able to make the decision.”

The patient decides to move forward with the reduction procedure.

Reflecting back, Dr. Hopkins shared, “What I've learned practicing high-risk OB is when you face a situation like this with a patient, it is impossible to know what decision that you would make if you were in that clinical situation … So just taking a step back and not necessarily trying to put yourself in the patient's shoes, but just stepping back and giving the information and just listening to the patient. I think as high-risk obstetricians, we're often the ones who have these stories and who see these patients, whether we're political or not, that's a life-saving procedure for us many times.”

The Complicated Decision-Making of a Molar Pregnancy and an Intrauterine Pregnancy Jan 18, 2023

A pregnant person is referred early in pregnancy to high-risk obstetrician Dr. Stacey Ehrenberg after an ultrasound detects an abnormally developing placenta. Dr. Ehrenberg diagnoses the patient with a molar pregnancy; a placenta that forms into a benign tumor with the potential to become cancerous. While the molar pregnancy will not survive, the patient also has a viable intrauterine pregnancy.

Faced with this diagnosis, Dr. Ehrenberg counsels her patient about the risks of continuing or discontinuing the pregnancy. If the decision is made to continue, the patient risks developing mirror syndrome, a life-threatening condition marked by hypertension and edema. There is also significant risk of bleeding if any of the abnormal tissue is removed.

If the decision is made to end the pregnancy, the patient faces the risks of any procedure done in a hospital; bleeding, infection, and damage to the surrounding organs, although this happens in less than 1% of cases. Regardless of the patient’s choice, Dr. Ehrenberg emphasizes that she and her team will support the patient, no matter what.

The patient decides to continue the pregnancy. Dr. Ehrenberg and team develop a care plan to track both the molar pregnancy and the intrauterine pregnancy with weekly ultrasounds and blood pressure measurements.

“I really watched her struggle throughout the pregnancy knowing that she knew that at some point the scale was going to tip and that this would no longer be safe for her to continue,” shared Dr. Ehrenberg. “Her hope, as was ours, was that she would be able to get far enough in pregnancy where the baby would be able to survive. She knew that this would probably be an extremely premature baby, but she was willing to take that risk to start her family.”

But at 19 weeks, everything changes.

“I didn't need vital signs. I didn't need to do a physical exam to know something wasn't right,” remembered Dr. Ehrenberg. “We got vital signs on her and I did a physical exam, and it was very clear to me that she had mirror syndrome and then we had to have the very difficult conversation that we knew that the baby was not yet viable, but it was no longer safe for her to remain pregnant.”

The decision is clear: the only viable option is dilation and evacuation.

But the procedure is not without serious complications and risks.

“... These pregnancy complications are so complex,” shared Dr. Ehrenberg. “The physical aspects of it, the emotional aspects of it, the financial aspects of it … So I really just would love to see more kindness towards other people, more tolerance towards other people, more understanding that we don't understand all the time where other people are coming from and what they've been through.”

Abortion as Healthcare (a Miniseries) Jan 11, 2023

Meet three obstetricians who perform an essential medical procedure: abortion. Learn about their patients and how abortion affects both physical and mental health. From a molar pregnancy to fetal chromosomal abnormalities, these stories illustrate the life-saving impact of abortion, and its necessity within healthcare.

Non-Specific Symptoms Lead to Complicated Diagnosis Dec 07, 2022

It starts small. A slight pain in the foot, followed by an achy shoulder. There's some fatigue. The type of non-specific symptoms that often go ignored … until they can’t be anymore.

A 37-year-old visits the family doctor, complaining of foot, shoulder and chest pain that progresses over weeks. And she's really tired. Otherwise, there’s nothing notable.

She's just a busy parent. Being tired is normal, right?

Sometimes that’s true, but in this case, this would prove to be a dangerous assumption.

She visits her primary care provider who decides to run X-rays. There’s nothing to note other than an expanded area of cartilage at the end of the sixth rib. The doctor doesn’t think much of it at the time, but this would prove pivotal to solving the case.

The patient is prescribed physical therapy, but it doesn’t help. It actually makes things worse.

“She's getting very fatigued to the point where she's having to lay down in the afternoons. She can't really do her full family activities,” shares Dr. Suzanne Jan De Beur, an endocrinologist with a specialty in metabolic bone disorders at Johns Hopkins University School of Medicine in Baltimore, Maryland. “She gets terrible pain … And then eventually she was found to have a left hip fracture and needed surgery to repair the hip fracture.”

This incredible progression — a hip fracture with no trauma at 39 years old — leads to more tests. She’s diagnosed with celiac disease, a wheat allergy that can cause weak bones from not absorbing vitamin D and other nutrients into the bones. This explains the fractures, but not the muscle weakness.

She’s compliant with her celiac therapy, but it keeps getting worse — to the point of needing a walker. This is when the patient sees Dr. Jan De Beur.

It’s at this time that a very small discovery leads to a very big diagnosis.

It also leads to many lessons — one being to not only zoom in on one specific symptom, but to zoom out on a case over time so you can put the puzzle pieces of non-specific symptoms together and find your diagnosis.

A Lump on the Skull and the Misdiagnosis of a Rare Bone Disease Nov 30, 2022

In 1964, Nancy, a 5-year-old, is having her evening bath when her parents discover she has a lump on the skull the size of a grapefruit. This would mark the onset of a mysterious and debilitating disease that researchers are still struggling to understand.

Over the next 40 days, medical professionals struggled to discover what was causing the lump on the skull. Each test seemed to exacerbate the swelling in Nancy's neck. In hindsight, that was a big clue, but it took doctors a while to recognize it.

Instead, what happened next was a common mistake when it comes to patients with this disease. Nancy was diagnosed with terminal cancer. Doctors said she had less than a year.

Yet, over the next few months, Nancy's condition didn't progress. She actually seemed to get better. Over the next few months, she was taken to a series of specialists. It was finally an oncologist who noticed something that was pivotal to her diagnosis ... her toes. Misshapen big toes — generally short and bending inward — are a hallmark of Nancy's disease.

While Nancy had several telltale signs of the disease, diagnosing rare diseases is difficult in part because they’re exactly that: rare.

“I can see how a practicing physician may feel a rare disease, ‘I'm never going to see it.’ But [this disease] is so striking that I think once you see someone with the disease … the image stays in your mind and even if someone, as a general internist or a pediatrician, never expects to see the case, you never know,” shares Dr. Eileen Shore, a medical researcher and geneticist specializing in musculoskeletal disorders at the University of Pennsylvania School of Medicine.

And early diagnosis of this — and other rare diseases — is crucial, not only for treatment but to avoid diagnostic tests that can harm patients. While Nancy did finally receive a definitive diagnosis, many of the earlier diagnostic tests were actually causing more harm than good.

“If you just have that in the back of your mind, that you have a vague image of what [it] is and see a patient who you think might have it,” says Dr. Shore, “to send a referral and get it confirmed, just think of the difference it would make in that family's life.”

Metatarsal Bone Fractures and a Rare Bone Disease Hiding in Plain Site Nov 23, 2022

A patient in her mid-50s complains of foot and leg pain. She's post-menopausal with low bone density. A classic case of post-menopausal osteoporosis.

Not exactly.

And it won’t start to become clear until it gets to the point of her having repeated metatarsal bone fractures.

Let’s go back a little. It’s 2005. Our patient visits her family doctor complaining of pain in her legs and feet. But the discomfort she's experiencing isn't your typical aches and pains associated with aging.

“She develops a lot of [foot and leg] pain … So much so that she required pain management for this pain and her gate started to become affected,” shares Dr. Katherine Dahir, a professor of medicine at Vanderbilt University, who specializes in metabolic bone disease.

Her gait becomes wobbly and she’s experiencing an acceleration of degenerative changes in her spine. An osteoporosis screening reveals she has low bone density. She’s diagnosed with post-menopausal osteoporosis and is treated with bisphosphonates, the standard of care for patients with osteoporosis.

And this is when things get much more complicated.

Although all signs show an improvement in bone density, she begins to experience metatarsal bone fractures, which is highly unusual with osteoporosis. And not only does she have these unusual fractures, the fractures will not heal.

“And so that's when you need to put your thinking cap on and try and figure out, why is this patient a treatment failure?” says Dr. Dahir.

To solve the case, the patient’s team studies her labs and finds a missing flag. “... It was called alkaline phosphatase, which is seen in a routine chemistry panel. Back at that time, it was only flagged if it was above the normal reference range because that usually indicates liver disease, but it wasn't flagged if it was below the normal reference range because that was considered to be non-significant.”

But this finding would prove to be very significant. Combined with new research at the time, it helped identify a diagnosis for this patient — showing the importance of medical research that leads to more treatment options and more hope for patients.

Hypophosphatemia and the Secret Locked in a Child’s DNA Nov 16, 2022

A toddler is taken to his pediatrician because his parents are concerned he might be small for his age. The pediatrician diagnoses him with knock knees, but there’s no cause for alarm.

Although the child doesn't have any other known medical conditions, something is happening in secret, inside his DNA that won’t be discovered until a diagnosis of hypophosphatemia is discovered some time later. And if this disease is ignored, it can quickly become deadly.

But back to that first appointment. “At that time, he had a rather normal diet, was taking [multivitamins] so his intake of vitamin D was at the recommended daily allowance,” shares Dr. Michael Levine, a pediatric endocrinologist at the Children's Hospital of Philadelphia. “And because he had no other medical disorders and no other conditions that were of concern, his pediatrician decided that they would just watch him to see whether he could outgrow his knock knees, and whether this might improve his overall growth.”

At the age of 7, there is little to no progress. He visits an endocrinologist. Nothing significant is found. At 10, an orthopedic surgeon operates on the child’s knock knees.

Two years later, he visits Dr. Levine for the first time. “When we first saw him, we were impressed by his prior history of knock knees, which had its onset in his toddler years, and we looked carefully at the evaluation that his pediatric endocrinologist had performed some years prior that disclosed normal levels of serum calcium, normal levels of PTH, normal alkaline phosphatase, and a normal serum 25-hydroxy vitamin D, which in the mind of the first pediatric endocrinologist had effectively ruled out rickets or osteomalacia.”

But one test hadn’t been done — a test for serum phosphorus level, and when the results come back showing hypophosphatemia, this becomes a key to the child’s diagnosis.

“When you have a child that doesn't respond as you might expect to calcium and vitamin D,” advises Dr. Levine, “you have to take that next step and begin to ask, could this be due to a genetic defect in the vitamin D system, or could it be a genetic defect in phosphate metabolism?”

As it turned out, the child’s disease was genetic, and this unlocked the path to treatment. And while everything worked out in the end, it’s hard not to think about how this story could have been very different had one simple test been run, or if genetics had been considered sooner.

Overlooked Diagnostic Test for Blood Calcium Levels Leads to Rare Diagnosis Nov 09, 2022

A 23-year-old presents to the emergency department with progressive symptoms. It starts with tingling in the fingertips that lead to leg cramps that turn into feeling like she’s turning into stone, frozen in one position with stabbing pain. And perhaps most troubling, she can't concentrate. In fact, the brain fog is so severe that she’s afraid to drive.

Over the course of three days, her life has been turned upside down.

She takes a taxi to the emergency department and is seen after waiting six hours. She provides a quick medical history, noting she recently had neck surgery for parathyroid overactivity — an important clue to her diagnosis.

Parathyroid glands produce parathyroid hormone that regulates the blood calcium level, which maintains bone strength and helps muscles and nerves function. Calcium levels in the blood have to be kept at a very specific level. Just like in your physiology lectures: HYPERcalcemia and HYPOcalcemia. And calcium levels that are either too high or too low can be deadly.

But in moving quickly in the emergency department, testing for serum calcium is overlooked. A patient with recent neck surgery has symptoms consistent with low blood calcium levels — why not check her calcium?

It’s true that in a chaotic ER things can be overlooked. But a lot of time, calcium isn't ordered because it's not part of the regular "electrolyte” or “chemistry” panel — it has to be added specifically. With computer systems and the way test panels like these are built, they can shape the thinking of physicians, putting certain symptoms front of mind, while others might get neglected.

Fortunately, a diagnosis was caught early enough for this patient that no long-term damage was done. But this case serves as a reminder that although rare diseases are rare, it doesn’t mean as a healthcare professional, you’ll never encounter them.

Mysterious Arterial Calcifications and One of the World’s Most Unique Patients Nov 02, 2022

An infant is born with no complications in a hospital in Los Angeles. Within days, that same baby will suddenly have mysterious arterial calcifications, making him one of the most unique patients in the world.

After being released from the hospital following the birth, within five days, the infant’s parents discovered the child breathing quickly, sweating and unable to eat. The child is brought back to the hospital and quickly transferred to UCLA for specialized care.

The situation quickly turns critical as the infant's heart begins to fail. His symptoms are also consistent with hypertension. The patient is immediately given traditional treatment for high blood pressure and placed on a ventilator, which stabilizes his condition while more tests are done.

X-rays come back showing an enlarged heart and signs of pulmonary edema. An echocardiogram then reveals that the child does not have a congenital heart abnormality — the most common cause of congestive heart failure. Period.

But the ultrasound reveals another clue. The infant has significant arterial acidifications in the arteries, in his chest, and also in his abdomen. It’s so thick that it’s restricting blood flow to the child’s heart.

Dr. Isidro Salusky, a Professor of Pediatrics who specializes in bone and mineral metabolism at the David Geffen School of Medicine at UCLA, explains, “It was very puzzling because first of all, when you see a newborn baby with congestive heart failure, the most common causes are defects in the heart … Why does this patient have arterial calcifications?”

Thanks to available medical research, Dr. Salusky and others on the medical team discover a rare genetic disease similar to their patient’s — one that causes over half the infants born with it to die within six months.

Even with this insight, it can take months to officially diagnose the child — time they don’t have. After much research and consulting with the team who wrote the available medical research, Dr. Salusky and team decide to move forward with treatment while they wait for the genetic testing results. The child stabilizes and the condition begins to improve.

The story doesn’t end there, though. This child’s ongoing battle would cause specialists to question what they thought they knew about this disease and its treatment — and to keep asking why.

Paediatric Seizures and The Race Against Time Jun 29, 2022

A toddler’s parents noticed him having muscle twitches before falling asleep and when waking up. They’re told nothing is wrong. This episode of DDx reminds us that sometimes when you hear hoofbeats, it really is a zebra.

Diagnosing a Complex and Mysterious Form of Paediatric Epilepsy Jun 22, 2022

A child was referred to a specialist on the suspicion he has pediatric epilepsy, a complicated and fickle condition. In this episode of DDx, we explore a case with several peculiar symptoms and diagnostic test results that baffled doctors. The answer may lie in genetic testing.

Mapping a Complicated Genetic History of Epilepsy Jun 15, 2022

A 5-month-old was brought to the emergency department with staring episodes. In this episode of DDx, we’re reminded that even when initial tests come back normal, keep thinking about the patient in front of you and probe parents for any new signs.

The Many Questions and Few Answers of a Rare Disease Diagnosis Jun 08, 2022

A toddler has episodes where his face changes, his arms shoot up, and he collapses. On this episode of the podcast, we address when rare disease diagnoses offer more questions than answers, and treatment options don’t lead to a cure.

Classic Symptoms of Rare Diseases and Avoiding Diagnostic Odysseys Jun 01, 2022

Rare diseases are … rare … which makes even textbook cases difficult to diagnose. In this episode, we’ll talk about the patterns and characterizations of a rare disease and how we can avoid diagnostic odysseys.

DDx Returns for Season Five May 25, 2022

Rare diseases are … rare … which makes even textbook cases difficult to diagnose. In this season, we’ll talk about the patterns and characterizations of a rare paediatric disorders.

The Importance of Genetic Screening Mar 23, 2022

Genetic screening is vital for early diagnosis and management of genetic diseases. In this episode, dig into how it works, how it can help treatments reach patients sooner, and how it informs traditional treatments like physical therapy.

Genetic screening works to determine which people might have a greater likelihood of developing a specific trait or disease, while genetic testing is concerned with testing an individual for a specific condition.

One method of screening takes the form of a DNA-sized probe to track when its identical sequence is discovered inside the cell. And once that matching code is found and additional tests confirm the match, genetic testing may be conducted, a diagnosis reached, and then treatment prescribed.

There are many different types of screenings, including prenatal genetic screening, which can range from testing amniotic fluid, drawing blood from the mother, and even taking a sample of embryonic cells formed by in-vitro fertilization.

A typical newborn screening looks for a number of conditions, including sickle cell disease, cystic fibrosis, and severe combined immunodeficiencies.

Newborn genetic screening has not only increased the potential for revolutionary treatments to be successful, but it has also dramatically improved other forms of care, like physical therapy.

Spinal muscular atrophy, or SMA, is a disease that affects approximately one in 11,000 infants. When SMA is identified early through screening, the role of physical therapy can be radically different than if the infant hadn’t undergone screening or been formally diagnosed with SMA.

In newborns who aren’t screened, or whose condition is not discovered so early, physical therapy plans may be designed to provide their atrophying muscles with physical support.

But when the condition is identified early, physical therapy can do so much more. It changes from care that focuses on making the baby as physically comfortable as possible to one that can potentially help them reach physical milestones.

Newborn genetic screening has dramatically changed the way specific diseases progress by providing personalized treatment. As treatments become more sophisticated and targeted, they can truly transform a child’s life, especially when administered early.

For more education on gene therapy, visit www.genetherapynetwork.com.

ALS, DMD and Adapting Treatment Mechanisms for Genetic Variations Mar 16, 2022

In this episode, we’ll dig into the different mechanisms by which gene therapy can potentially treat specific genetic diseases – such as amyotrophic lateral sclerosis, or ALS, and others.

In 1993, a multinational group of scientists and doctors solved a medical mystery 150 years in the making.

And they did it, in part, by examining the genealogy of a particular family in Vermont. In 1835, a farmer named Erastus Farr died of a mysterious illness characterized by a progressive weakening of his muscles followed by paralysis and respiratory failure.

Thirty years later, his descendent Samuel Farr died of the same condition, as did four of Samuel’s eight children, the youngest at the age of 27.

By 1880, the Canadian physician Sir William Osler had studied the Farr family phenomenon and concluded that they all suffered from a newly identified disease known as amyotrophic lateral sclerosis.

But how could this frightening condition be passed from one generation to the next?

Over the next hundred years, scientific interest in the disease grew, especially after the legendary baseball player Lou Gehrig died of the disease in 1941.

But there was still a mystery: while 90% of ALS cases are considered sporadic – meaning there is no hereditary connection – the other 10% of cases seemed to run in families, like the Farrs.

After the dawn of the genetic age, scientists began to suspect a gene variation was at the heart of the mystery. And then finally, in 1993, scientists including Robert Brown at the University of Massachusetts medical school, who studied the Farr family and others while also investigating the human genome, uncovered the answer.

In some ALS patients, a variant of a single gene, called SOD1, can cause a buildup of toxic proteins in the brain, leading to the various symptoms that characterize the disease. In this case, the goal of gene therapy is to block or silence the abnormal production of a protein.

And solving that mystery has paved the way for gene therapy, perhaps someday soon, to provide the first known treatment for familial ALS.

For more education on gene therapy, visit www.genetherapynetwork.com.

Gene Therapy in Action: Adeno-Associated Viral Vectors Mar 09, 2022

Adeno-associated viral vectors, or AAVs, are the tiny shells of viruses. And today they are the most common vessels for delivering gene-based therapies. In this episode, we’ll launch into the past, present, and future of AAVs.

Imagine a rocket ship blasting off from Earth with cargo bound for a distant space station, and you have a pretty good idea what adeno-associated viral vectors are all about. But instead of ferrying hardware and supplies, AAVs carry genes.

It’s an achievement nearly six decades in the making. That might seem like a long time to tinker with something smaller than the tiniest single-celled organism. But just like building a rocket ship destined for the deep reaches of space, the development of AAV vectors required patience, persistence, and a few leaps of faith.

In the era before DNA sequencing and gene cloning, scientists in the 1960s realized that adeno-associated viral vectors could be a window into understanding genetic variations in viruses – and eventually other organisms, too.

The fact that AAVs were immunologically distinct from other viruses made them curious things.

So in the 1970s, AAV research took off in three directions. One determined that the simple AAV DNA could be rewritten and edited in a lab. The second found that although these small viruses can infect humans, they don’t replicate without a “helper virus” (such as adenovirus). In the absence of another virus, they remain latent, and appear to be of little threat to human health. The third investigated whether AAVs could become vectors for transferring genes from one organism to another.

This all culminated in 1978, when the first cloned AAV was generated and was successfully transferred to a cell of the E. coli bacterium, where it produced 50 new colonies of AAVs.

So now we had proof that adeno-associated viruses could be artificially produced, that they

could be hollowed out and filled with other genetic material, and that they could potentially be

a vector for delivering genes without harming their new host.

By the 1980s, we had the capability to build lots of viral rocket ships and fill them with genetic cargo, we just needed a destination to send them. Enter the burgeoning field of gene therapy, with its focus on developing treatments for genetic diseases like cystic fibrosis, hemophilia B, Parkinson’s, and more.

Research has continued and today, adeno-associated viral vectors are a mainstay of gene therapy development. While progress is necessarily slow, gene therapy is a science that is aiming for the stars. And with AAV vectors, they are now within our reach.

For more education on gene therapy, visit www.genetherapynetwork.com.

The Future of Gene Therapy and Genetic Diseases Mar 02, 2022

Peek into the future of gene therapy and its capacity to treat – maybe eliminate – genetic diseases like cancers and hemophilia. Plus, the potential to reverse the effects of aging.

It’s a future scientists have been working toward for years: How to treat complex health problems with gene therapy. And researchers have been making progress. Diagnoses once thought to be fatal are now being looked at in a new light.

This is a welcome sight for physicians, caregivers, and – most of all – for the patients living with these genetic diseases.

One disease that’s impacting lives worldwide is cancer. Nearly 40% of the world’s population will be diagnosed with it at some stage of life.

Typically, cancer treatment takes three forms: chemotherapy, surgery, or radiation therapy. Targeted drug therapies also exist, which work by identifying and attacking cancer cells individually.

But the treatment that many believe has the most potential is immunotherapy.

Immunotherapy uses a patient’s immune system to target and destroy cancerous tumors. And a specific type of immunotherapy known as Chimeric antigen receptor (or CAR) T-cell therapy has particular promise.

Over the last few years, progress with this new class of gene-based treatment has accelerated.

CAR T-cell Therapy is when a patient's own immune cells – the white blood cells called T cells – are genetically altered to target and attack a specific cancer within the body. These cells are first removed from the patient’s blood. Their genes are then altered to produce proteins called CARs, which allow the T cell to better recognize – and attack – specific cancer cells. When the altered immune cells are reintroduced into the patient's bloodstream, these proteins latch onto both healthy and cancerous cells, destroying the cancerous cells while leaving the healthy cells unharmed.

CAR T-cell Therapy has the ability to revolutionize cancer treatment and prevent relapse, as these cells can potentially continue to attack cancerous cells in a patient’s body for years. But it’s not a solution for everyone. Only about 40% of patients have long-term responses.

But if this therapy achieves what scientists believe it can, chemotherapy could be a thing of the past, and when it comes to the future of gene therapy and genetic diseases, there's reason for optimism.

For more education on gene therapy, visit www.genetherapynetwork.com.

How Does Gene Therapy Work? Correcting Disease-Causing Genetic Variations Feb 23, 2022

Not all genetic variations are associated with threats or harms to human health. Some even protect us, such as genetic variations that have been shown to make bones harder or the heart more impervious to disease. But while some genetic variations are positive, others can cause or contribute to disease.

In this episode, we answer the question of how does gene therapy work, and learn how gene therapy replaces and repairs certain gene variants, and is changing the trajectory of genetic diseases.

For several years, Dr. Jean Bennett at the University of Pennsylvania’s Department of Ophthalmology Center for Advanced Retinal and Ocular Therapeutics investigated the possibility of replacing gene variants in the retina – which cause blindness – with copies of healthy ones.

After successfully treating blind puppies, Dr. Bennett and her colleagues turned their attention to treating human eyesight.

The retina turned out to be a good target site for gene therapy. In most parts of the human body, our cells keep dividing after we’re born. But not the rods and cones in our retina – these photoreceptor cells don’t regenerate.

A major obstacle in the development of gene therapy is the tendency of cloned genes to get lost in the process of cell division before they have a chance to integrate into the host DNA. Because retinal cells don't divide after birth, the cloned gene may be expressed for a prolonged time

In 2017, after decades of painstaking research, building on the efforts of countless scientists throughout history, Dr. Bennett and her colleagues had the evidence that gene therapy may be used to treat genetic conditions in humans.

Since then, gene therapy has undergone giant leaps in the treatment of specific diseases.

And record numbers of gene therapy trials are ongoing, including potential treatments for conditions such as sickle cell disease and Parkinson’s disease.

It’s just one of many ways that the field of gene therapy is poised to change the world in the years to come.

For more education on gene therapy, visit www.genetherapynetwork.com.

A Brief History of Gene Therapy and the Discovery of DNA Feb 16, 2022

In this episode, we explore some of the major scientific findings – like discovering DNA – that set the stage for the development of gene therapy and its groundbreaking potential when it comes to the treatment of genetic diseases.

The very idea of gene therapy wouldn’t be imaginable had two pairs of pioneering scientists not bonded decades earlier. In 1951, a young chemist named Rosalind Franklin and her colleague Maurice Wilkins at King’s College in London were using X-ray crystallography to try and perceive the properties of a theoretical molecule known as deoxyribonucleic acid.

At the time, many scientists believed that all the genetic information about living organisms was contained in a molecule called DNA. But no one had figured out exactly what it was, or what it looked like.

After attending a presentation by Franklin, James Watson – who was also studying the topic – connected with Francis Crick. Crick had been studying the concept of base pairs – the idea that nucleic acid is composed of chemical bonds between not one but two sets of molecules, each supporting the other, much like the two sides of a ladder support the rungs in between. Excited by their shared passion, Crick and Watson in Cambridge began to build models of possible DNA structures, trying to figure out just how all the pieces fit.

Eventually, Franklin, Wilkins, Watson and Crick’s efforts joined, and DNA was discovered. Then, in the 1970s, DNA was successfully transferred from one life form to another.

Less than 50 years after Crick, Franklin, Wilkins, and Watson first showed us what this molecule looks like, genetic engineering gave us the ability to reprogram it when it isn’t working.

Scientists and doctors began to dream big: could this technology eventually cure all genetic diseases?

There was still work to be done. But, like a tiny plasmid loaded up with recombinant DNA, we were on our way.

For more education on gene therapy, visit www.genetherapynetwork.com.

DDx is Back for Season Four Feb 09, 2022

Take a deep dive into one of the most awe-inspiring medical innovations of our time: gene therapy.

It's comparable to some of the greatest scientific explorations ever undertaken. Like landing astronauts on the moon or sending spacecraft toward the edges of our galaxy.
Except, instead of probing the vastness of outer space, this season, we’ll explore the infinite universe inside the tiny molecules of our DNA, and look at medical technology with the potential to reshape our approach to treating many genetic diseases.

Thousands of lives could be saved and countless more changed with gene therapy.

Searching for zebras Sep 08, 2021

Few patients. A scarcity of literature. Working in rare disease can feel like you’re standing at the edge of an abyss with just a flashlight in your hand. And someone’s life depends on you--Meet the doctors who spend their time searching for zebras, and find out what motivates them.

Head to Figure1.com/ddx where you can find full show notes, photos, and speaker bios.

A fractured childhood Sep 01, 2021

When a baby girl is born with two broken femurs, doctors don’t notice the bluish-grey discoloration of her sclera, her bowed and shortened legs, or her larger-than-normal head. And it will be months before they piece together the puzzle

Head to Figure1.com/ddx where you can find full show notes, photos, and speaker bios.

Hunting for a diagnosis Aug 25, 2021

After a patient in his early 30s develops muscle weakness so severe he requires a wheelchair, he’s diagnosed with multiple sclerosis, and starts treatment for the disease. But when a bone scan reveals multiple fractures, his physicians start to question their original diagnosis.

Head to Figure1.com/ddx where you can find full show notes, photos, and speaker bios.

When the fever breaks Aug 18, 2021

A one-year old boy is brought to his doctor with a history of febrile seizures, odd movements, and developmental delay. His seizures continue, but the fevers stop. And doctors realize they’re in a race against time.

Head to Figure1.com/ddx where you can find full show notes, photos, and speaker bios.

Code blue Aug 11, 2021

“Code blue, unit 305. Code blue, unit 305.” After an 8-year-old boy with recurrent episodes of rhabdomyolysis is hospitalized for treatment of a rare inherited disease, his condition quickly deteriorates.

Head to Figure1.com/ddx where you can find full show notes, photos, and speaker bios.

The forgotten disease Aug 03, 2021

A 35-year-old man thought he had outgrown the rare disorder which he was diagnosed with as a child. But as his movement becomes increasingly limited, he realizes that he never escaped it, and now there’s more than just his mobility at stake.