DDx

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.