DDx

Health & Fitness
**DDx**

DDx is medical shorthand for differential diagnosis, and this is a podcast about how doctors think and learn on the job. It’s hosted by Dr. Raj Bhardwaj and is produced by Figure 1, the global knowledge-sharing platform for medicine.

Latest Episodes:

Abortion as Healthcare (a Miniseries) Jan 11, 2023

Show notes

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.

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

Show notes

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

Show notes

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

Show notes

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

Show notes

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

Show notes

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

Show notes

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

Show notes

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

Show notes

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

Show notes

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.

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