The phone from Clinical Genetics came at 5:12 p.m. on April 10, 2018. Grace Wilson-Rabel remembers the exact time and date because it’s the moment that changed her life.

Candace Gamble, M.D., is a clinical geneticist with Cook Children’s, and the call was to let Grace know her daughter’s diagnosis.

Wilson was a secretary for Cook Children’s NICU and she motioned for her charge nurse to say she needed to take the call.

“OK, we received Austyn’s test results back. Her test is positive.”

Austyn had been diagnosed with neurofibromatosis type 1 (NF1), a genetic disorder that affects 1 in 3,000 people throughout the world. NF1 impacts children in many different ways, including light brown skin spots, neurofibromas (small benign growths) on or under the skin and/or freckling in the armpits or groin.

About 50 percent of people with the condition have learning challenges. Health concerns also include the softening and curving of bones, and curvature of the spine (scoliosis), and occasionally tumors may develop in the brain, on cranial nerves or the spinal cord.

While these tumors are usually not cancerous, they can cause health problems by pressing on nearby body tissues.

Following the diagnoses, Grace immediately felt cold fear run through her entire body and she broke down in tears.

After all, everything had changed.

Austyn was born Jan. 23, 2017.

Grace’s pregnancy was normal until her thirty-fifth week when she began to experience high blood pressure. Because it continued to be elevated, she was induced at 37 weeks. Austyn was born weighing 6 pounds, 12 ounces.

“There were absolutely no signs that she had a genetic condition hiding inside of her,” Grace said. “At 2 days old, we had her newborn check-up and discovered that her bilirubin was high.”

At 2 weeks old, Grace noticed her daughter was working hard to breathe and made a “horrendous noise” every time she inhaled, so back to the pediatrician’s office she went with her daughter.

Following three more visits to the Emergency Department at Cook Children’s, Grace made an appointment with Pulmonology where Austyn was diagnosed with laryngomalacia, a congenital softening of the tissues of the voice box, or larynx, above the vocal cords. This new diagnosis caused a whole other set of issues. Austyn’s suck/swallow/breathe coordination was off, which caused failure to thrive and a hospitalization at 7 months.

Due to her low weight and delayed development, Austyn was tested for cystic fibrosis.

“Thankfully that test came back negative, but we were placed in physical therapy because despite working with her every day, she did not crawl until 11 months and did not walk until 19 months,” Grace said. “We would find out later, with her diagnosis, that this is all very common for kids with NF.”

At 3 months, Grace noticed Austyn had three brown spots on her abdomen.

“I didn’t really think too much of it other than I thought they were cute birth marks,” Grace said.

At her 4-month checkup, Grace pointed out the spots to her pediatrician, Joyce Rafati, M.D. Dr. Rafati looked at them and said she thought it could be neurofibromatosis, but it was too early to tell.

By the age of 10 months, Austyn had 13 spots. Dr. Rafati referred Austyn to be seen by Dr. Gamble in Genetics to test for NF.

“The earliest we could be seen by the geneticist was January 29, 2018 – which was four months out,” Grace said. “The hardest part of this whole journey is patience. The wait time to see a specialist always feels so far away and then after the specialist visit we are left in limbo because there are so many ‘wait and see’ moments with NF.”

Austyn received a simple blood draw to test for the genetic condition, but it would take six or more weeks for the results. The test is expensive and has to be approved through insurance, which took another four weeks.

Once she received the approval, she took Austyn to the lab at the Dodson and had Austyn’s blood drawn on March 1, 2018.

Six weeks after the test, Grace received the phone call with the results.

“Processing that was one of the hardest things I’ve ever had to do,” Grace said. “I’m still processing it to this day. You have to go through a grieving process that sometimes takes months to years. You may grieve it your whole life but you have to be strong and you have to push through. NF1 brings lifelong doctor appointments and ‘what if’ questions. And, every day that there isn’t something going on and you’re not in the doctor’s office is a win.”

Grace said what helped her get through the most difficult time of her life was her husband, George. “He’s been my rock through this,” Grace said.

A few months later, Grace and George took Austyn to meet her new neurologist, Jeff McGlothlin, M.D.

“He was amazing, so gentle and thoughtful with Austyn and her condition,” Grace said. “And with talking to us. He answered all of our questions and gave us an idea of what the game plan would be.”

Austyn was supposed to have surgery to fix her airway a couple of weeks after her neurologist appointment so Dr. McGlothlin decided to piggy back on the surgery and do her first MRI to test for optic nerve gliomas the same day so she would only have to be sedated once. Gliomas are non-cancerous brain tumors that can affect a child’s vision.

“The day of the surgery came and we anxiously handed our sweet 18- month-old baby over to the arms of the doctors and nurses,” Grace said. “We knew she was in great hands but it didn’t take away that fear and sadness of what she is having to go through.”

About four hours later Austyn was out of surgery and recovering in the PICU at Cook Children’s. All went well. She had a great night and the next morning she was in good spirits and eating. The MRI was the last thing on Grace’s minds.

Around 10:30 in the morning, while still at Cook Children’s, Grace received a call from the neurologist’s office.

“I didn’t even think that they would be calling me to tell me bad news, I just thought they might be calling to tell me everything looked great. I was wrong,” Grace said. “The woman on the other end said, ‘Dr. McGlothin wanted me to let you know that there are two optic gliomas.’ I couldn’t even breathe. ‘What?’ I asked, choking back tears. She repeated the news and all I could say was, ‘This has been the worst year,’ and I sobbed and sobbed.”

Grace watched Austyn sleeping peacefully. She was so small and innocent and unaware that she had something so concerning inside her “precious little head.”

“Austyn has had a few more eye appointments and another MRI and I am happy to report that as of today her vision is unaffected and her tumors are stable,” Grace said. “We hope and pray that they stay this way. Her neuro-oncologist is pretty confident that she will never need treatment. Since these tumors are inoperable the only treatment option is chemotherapy.”

Grace said Austyn has been through more needle sticks, tests, hospitalizations, etc. in her short two years of life than most adults have. But throughout the process, Grace said she couldn’t be more grateful for Cook Children’s and the team that has taken care of her daughter since that day when her life changed: her pediatrician Dr. Joyce Rafati, gastroenterologist Danny Rafati, M.D., endocrinologist Teena Thomas, M.D., neurologist Dr. McGlothin, neuro-oncologist Jeffrey Murray, M.D., her ENT Michelle Marcincuk, M.D., and pulmonologist Nancy Dambro, M.D.

“Austyn has rocked everything like a champ,” Grace said. “She knows when they want to listen to her lungs, heart and belly, where the stethoscope goes. She knows where the blood pressure cuff goes and holds her arm or leg out for it. She never complains. And all of her doctors and nurses are her friends.”

Two new studies emphasize the dangers of teens using e-cigarettes

The studies published in Pediatrics magazine showed teens who only vape have the highest level of cancer causing chemicals in their bodies and the e-cigarettes are associated with future smoking in teens.

The researchers from the University of California, San Francisco challenge the idea that e-cigarette vapor is safe. They found that teens who use e-cigarettes are in danger of inhaling cancer-causing chemicals, especially in fruit flavors.

“The presence of harmful ingredients in e-cigarette vapor has been established; we can now say that these chemicals are found in the body of human adolescents who use these products,” authors wrote.

The UC San Francisco researchers found that adolescents who smoke e-cigarettes expose themselves to a high levels of the potentially cancer-causing chemicals also found in tobacco cigarettes, even when the e-cigarettes do not contain nicotine.

"Teenagers need to be warned that the vapor produced by e-cigarettes is not harmless water vapor, but actually contains some of the same toxic chemicals found in smoke from traditional cigarettes," said lead author Mark L. Rubinstein, MD, a professor of pediatrics at UCSF. "Teenagers should be inhaling air, not products with toxins in them."

This was the first known study to report on the potentially cancer-causing compounds in the bodies of adolescents use e-cigarettes, according to UCSF. The lists of compounds include acrylonitrile, acrolein, propylene oxide, acrylamide and crotonaldehyde.

Another study from the same institution and also published in Pediatrics found that “e-cigarette use is more likely to encourage youth smoking that to divert youth form smoking.”

The team found those who had ever used e-cigarettes were significantly more likely than never users to have smoked at least 100 cigarettes at follow-up, have smoked during the past 30 days or both.

To learn more about e-cigarettes, we talked to Don Wilson, M.D., an endocrinologist and an Endowed Chair of Cardiovascular Health and Risk Prevention at Cook Children’s.

What do e-cigarettes do?

E-cigarettes are designed to simulate the act of smoking and deliver nicotine without the toxic chemicals produced by burning tobacco. The use of nicotine, however, is highly addictive. Recent research suggested nicotine exposure may also cause the brain to become addicted to other substances. Vapor from some e-cigarettes has also been shown to contain known cancer producing and toxic chemicals, such as diethylene glycol and nitrosamines, as well as small particles of toxic metals. Although not well studied, there is the potential for second hand exposure by others in the environment.

How do e-cigarettes work?

E-cigarettes are smokeless, battery operated devices designed to deliver nicotine mixed with a variety of flavorings (fruit, mint, chocolate, etc.) and other chemicals via an inhaled aerosol. They typically resemble regular tobacco cigarettes, cigars, pipes or everyday items like pins or USB memory sticks.

Most e-cigarettes generally contain three components: a cartridge that contains a liquid solution containing various amounts of nicotine, flavoring and other chemicals, a heating device or vaporizer, and a rechargeable battery. Puffing on the e-cigarette activates the battery powered heating device causing the liquid to vaporize. The vapor is inhaled by the user. E-cigarette vapor may include metals, rubber and ceramics which may be aerosolized and have adverse health effects.

Are e-cigarettes safe?

Although a limited number of studies have been conducted, the safety of e-cigarettes has not thoroughly been evaluated in scientific studies.

Here are a few points to consider:

• Nicotine is highly addictive and has negative effects on brain development from infancy to teens.
• Potential consequences of using e-cigarettes among youth include nicotine addiction, withdrawal and the potential for overdose.
• The use of a variety of flavoring in the liquid solution of e-cigarettes has created concern for accidental ingestion by smaller children.
• With the rapid increase in use of electronic nicotine delivery systems (ENDS), users and nonusers are exposed to the aerosol product. While e-cigarette aerosol may contain fewer toxins than cigarette smoke, studies evaluating whether e-cigarettes are less harmful than cigarettes are inconclusive.

Bottom line: e-cigarettes are often promoted as safer alternatives to cigarette smoking. Although very little is known about their safety, they are increasingly being used by youth and young adults.

What about second hand exposure?

The potential exists for secondhand nicotine and other tobacco-related toxin exposures to others. Studies have shown that e-cigarettes are a source of secondhand exposure to nicotine but not to combustion toxins. Thus, while use of e-cigarettes in indoor environments may involuntarily expose nonsmokers to nicotine, it does not seem to expose them to toxic, tobacco-specific combustion products.

What does the American Academy of Pediatrics recommend?

To protect the health of youth, the American Academy of Pediatrics has made the following recommendations:

• Sales of e-cigarettes to minors (under 18 years of age) should be prohibited.
• Candy and fruit flavored e-cigarettes, which encouraged youth smoking initiation, should be banded.
• To avoid exposing others to potential harm, laws should mandate smoke-free environments which include e-cigarette vapor.
• To prevent poisoning, all e-liquids should be required to be sold in child-proof packaging.

Almost half of the people who participated lost an average of 30 pounds, went into remission and were no longer diagnosed with diabetes. They did not take any medications during this time and relied solely on weight loss. “Remission of type 2 diabetes is a practical target for primary care,” the authors of the paper wrote.

The participants in the study were on a liquid diet of 825 to 853 calories daily for three to five months and then were reintroduced to solid food, while maintaining a structured diet over the course of a year.

All the individuals who participated in the study were adults (20-65 years of age).

Joel Steelman, M.D., an endocrinologist at Cook Children’s, said that weight loss has been especially effective in treating adults, whether through diet or after weight loss surgery, and can lead to de-escalation of treatment or stopping therapy. This has been especially true in adults, whether through diet or after weight loss surgery.

Dr. Steelman said children with type 2 diabetes will also benefit greatly from weight loss, but an extreme low calorie diet, like the one the participants in the adult study were on, is a bit more of a concern in a still growing, developing child. Dr. Steelman said pediatric endocrinologists focus on eating a healthier, lower calorie, lower carbohydrate diet, while also stressing the child becomes active.

“Weight loss and improved diet often leads to de-escalation of treatment for children – stopping insulin often and sometimes stopping oral medication,” Dr. Steelman said.

But a child can’t make extreme lifestyle changes without the entire family buying in and everyone in the household living healthier. A child needs the full support and active involvement from all family members. Therapeutic lifestyle changes need to last a lifetime.

“It’s essential for the parents to be extremely involved. You to have buy-in and support from the family,” Dr. Steelman said. “There’s often type 2 diabetes in one of both parents. It’s a no-brainer that the whole family will experience some benefit, whether immediate or future, from improving food choices and increasing activity. It’s critical to understand that type 2 diabetes is a deadly disease, and is associated with earlier and more frequent cardiovascular disease and premature mortality than type 1 diabetes mellitus.”

A parent’s natural protective instinct would be to prevent the possibility of broken bones and limit high risk activities. However, regular physical activity is important for good bone health. Strength, balance and coordination gained from regular physical activity help prevent fractures. Daily movement – walking, standing, running – all stimulate bones to take up calcium and get stronger.

1. Is my child’s broken bone bad luck or something more?

Children with weaker bones containing less calcium are at higher risk for bone pain and broken bones. There are many causes and conditions leading to overall weaker bones in children. Some of the causes are very obvious while others are challenging to detect.

Diet is an obvious first thought for many parents as a cause of weak bones. Today’s children face a minefield of diet challenges. Most parents know that a poor diet carries a high risk of obesity, but many of the same poor diet choices also add risk for weaker bones.

A diet which is low in calcium and vitamin D deprives bones of vital raw materials for bone health. Drinking excess sugar containing soft drinks is already a risk for obesity, but it also is a risk for weaker bones. Soft drinks are high in the mineral phosphorous which binds calcium and make it unavailable for building bones.

Eating a bone healthy diet is not a full guarantee for good bone health. Digestive conditions such as celiac disease, inflammatory bowel disease, or liver disorders damage the intestines ability to absorb calcium and vitamin D properly.

Loss of mobility from neuromuscular conditions such as spina bifida, cerebral palsy, and muscular dystrophy, and spinal cord injury with paralysis remove the important positive effect of movement and standing on bone health. Most children with these conditions have weaker bones.

There are a number of rare genetic conditions, osteogenesis imperfecta being the most recognized, that are linked to weak bones and frequent bone breaks. A key clue often seen with a genetic condition causing weak bones is early appearance of broken bones, sometimes even before birth.

Lastly, certain medications can have a negative impact on bones. Glucocorticoids like prednisone are used to treat inflammation in the body. However, long-term use of this group of medication weakens bones. There are now recent reports of osteoporosis in adults with excessive use of proton-pump inhibitors which treat acid reflux. It’s not known yet if the same risk might happen in children.

2. When should a parent worry about a child’s broken bone?

Children who are already at risk for a broken bone need close monitoring and prevention treatment with calcium and vitamin D.

There are several expert recommendations on investigating broken bones in otherwise healthy children. A child needs further investigation if he or she has any of the following in their bone health history:

• Two long bone fractures before age 10.
• Three long bone fractures before age 19.
• Any vertebral collapse fractures.

3. How is bone health checked in children?

A careful medical history and examination are important first steps in determining risk for a child. Lab tests, both blood and urine, measure important levels in the body including calcium and vitamin D.

A special X-ray test called a DXA scan is used to measure the calcium content in bone and is an important step in determining bone health and risk for fracture. Interpreting the DXA results in children is more challenging than in adults and requires a pediatric specialist with expertise.

4. What can a parent do to insure healthy bones in their child?

Make sure your child has plenty of calcium and vitamin D in his or her diet. Milk and dairy are the prime sources of calcium in the diet. Three servings of dairy per day is important for children 4-8 years old. For the lactose intolerant child, there are lactose-free alternatives available which deliver necessary calcium. A parent should speak with their child’s doctor about calcium and vitamin D supplements if continued concerns about adequate amounts in the diet.

Get your child outside and get them moving. Sunlight exposure is key in the body’s internal production of vitamin D (but wear sunscreen). Movement of muscles, running, and just standing all help stimulate building of healthy, strong bone.

Contact your child’s doctor if he or she has a medical condition putting bone health at risk or if there are unexplained bone pain or fractures.

They could all learn a lesson from a young woman named Marissa Heintschel.

I learned about Marissa during one of my recent searches for news about my field, pediatric endocrine. The news story featured students in the Frisco high school independent study and mentorship program.

One of the students in this program was Marissa, who had chosen pediatric endocrinology as her focus of study. I reached out to her via Twitter to learn more about her experience in the program and was very impressed by her story.

Like many in my field, she had a personal connection to pediatric endocrinology, having been diagnosed with Type 1 diabetes at 7 years old. She shared with me her passion for medicine and her experience she’s gained and the research that she did during her year in the program.

I asked how her experience had changed her view of children living with a chronic condition such as Type 1 diabetes. Her answer gave me a fresh, personal perspective on challenges of life with this chronic condition:

“I have always made it very public that I had Type 1 diabetes,” she said. “I went through the whole phase of trying to hide it away from people. I wish I would’ve realized sooner the importance of taking care of myself because when I was 14 or so I was stupid and thought that if I ignored my diabetes it will go away and that I could run away from my problems.

I wear an insulin pump. I’ve been called things like a robot and people in random places will just stare at me.

There was once this kid in my class sophomore year that I started to become really good friends with. One day I asked where he went and someone said that he went to go take his shot because he was diabetic. It was so surprising to me because no one really knew he was diabetic.

So then I started talking to the kid more and more about his diabetes and he just opened up to me and was able to talk about his problems that only people like us could understand. After he opened up to me, he told me how thankful he was that we had grown closer because he now felt he had the confidence to tell people about his diabetes.”

Marissa’s story got me to thinking about the importance of sharing about having Type 1 diabetes and how difficult it can be. I, and others on the Cook Children’s diabetes team, speak to children and their families about sharing about their diabetes when we meet with them at Cook Children’s during the difficult period of initial diagnosis.

• Support
• Safety

These are the two important reasons for S haring with others about having diabetes.

Sharing opens the opportunity to understand better the routine (checking blood sugars, taking shots, meal planning, etc.) that someone with Type 1 diabetes must do daily. Sharing opens up opportunity for support and encouragement. In Marissa’s case, it may be the opportunity to encourage and support someone else with Type 1 diabetes.

Marissa’s story also shows that sharing does open up vulnerability and risk. I asked Cook Children’s endocrine clinical therapist, Kim Cox, how she talks to children and families about sharing about diabetes.

“I usually talk to them about how ‘secrets’ tend to make other kids think it’s a bigger deal.

Why don’t they want others knowing? Are they

…. embarrassed?

... afraid of bullying?

... etc.

Being honest (but brief) about answering peers questions seems to work best. For example, I have diabetes, I have to take medicine when I eat now. We then discuss those issues.”

I use the example of a kid who gets glasses in school. In the beginning, you notice every time you see them, peers will comment and possibly even say mean things, but as time goes on, their glasses just become part of them and you only notice if they don’t have them on. Other kids move on to something else.

Safety is important because even in the best of cases diabetes care is unpredictable. High or low blood sugars affect mood and behavior. In particular, a low blood sugar can cause erratic behavior and eventually unconsciousness. Knowing about the diabetes allows others to have the advantage of understanding and help someone with Type 1 diabetes.

Marissa has a future of opportunity ahead of her and will be starting college at my alma mater, Texas A&M, where she will major in biomedical engineering and pre-med. She told me that she chose biomedical engineering because the potential that technologies such as stem cell research and tissue engineering for a cure for diseases such as diabetes. Being a doctor is her dream, and I think that she has learned a lot from her experience that will help her in the long journey to a field in medicine.

In the field of endocrinology, however, there has been ongoing serious scientific study regarding risk of diabetes and metabolic syndrome linked to artificial sweetener use. Unfortunately, a definite answer hasn’t been reached to this question. One of the primary barriers making scientific investigations difficult is the fact that many of those using AS are already obese and at high risk for diabetes and metabolic syndrome.

A number of theories have been offered by those who believe the link between AS and diabetes/metabolic syndrome is real. Perhaps, those using AS over-estimate the calorie savings from AS and over-eat. Perhaps, the craving for sweetness is increased with AS use leading again to extra sugar-rich calories in the diet. Perhaps, there is premature loss of satiety (that sense of fullness with a meal) when AS is used leading to earlier return of hunger. There are many other theories as well with individuals lining up in support or against the theories.

A newly published article from last month adds more information on the possible link of AS to diabetes/metabolic syndrome. The scientific study investigates the effects of AS in both mice and humans from a unique perspective and made national headlines.

The most provocative part of the article deals with an 11 week investigation in mice. The mice were given artificial sweeteners (saccharin, aspartame, sucralose) along with a regular diet. They were tested at the start and at the end of the experiment. The mice given AS had an abnormal, pre-diabetic response to a large meal of glucose (sugar) compared to mice given water or sugar-water. A smaller number of mice in the study were tested with a combination of saccharin and a high fat diet and showed a pattern of pre-diabetes in blood testing within 5 weeks. The research reported in humans in this study was less compelling and showed pre-diabetes changes in some but not all of the human research participants.  

What was the reason offered by the researchers explaining pre-diabetes changes seen in AS use in their research? Gut microflora and the changes they believe occur in the digestive system from absorbing artificial sweeteners. I know you want to know more about gut microflora, right?

Gut microflora refers to the many kinds of bacteria living the digestive system. Our knowledge about the kinds and roles of these helpful bacteria continues to increase. Scientists have known for a while that these bacteria help make some essential vitamins such as vitamin K and help keep bad bacteria from multiplying too fast.

The research reported drastic changes in the types of gut microflora in all the mice fed artificial sweeteners and in some of the human subjects. The unique theory offered by their research is that changes in the gut microflora caused by AS exposure were responsible for the pre-diabetes seen in the research. In other words, the artificial sweeteners changed the numbers (increasing some and decreasing others) of the many different microflora in the bodies of the mice.

As a pediatric endocrinologist, I welcome the ongoing investigation of the safety of AS use. For many of the children and their parents whom I care for there is a problem. Excess dietary sugar represents a significant fuel to the obesity epidemic and must be managed. Dietary use of AS is almost essential in those with type 1 diabetes to help in maintaining stable blood sugars. For those with type 2 diabetes, AS may help in managing daily calorie intake and reversing obesity.

It is probably overly optimistic to believe that AS are completely without impact on the body. The real ongoing scientific challenge is gaining the proper perspective on their health impact. Proper perspective is very important. For instance, the AS exposure in the mice studied was maximal, which would be comparable to drinking 19 diet drinks per day which is very unnatural.

The big, unanswered question brought up by this research is what could be the long-term effects in those who eat or drink much lower levels of AS. I personally decided within the past year to reduce my AS intake as part of an overall decision to eat healthier. This study doesn’t persuade me yet to eliminate AS completely (I love Diet Coke^® too much). My best advice after reading this article is moderation and continued focus on a healthy diet.