Imagining a Vision for Genetic Medicine

Over 4 decades of Compassionate Care and State-of-the-Art Technology

Think about the impact of genetics on today’s healthcare. You can hardly go a day without seeing news of a novel gene for a common disease or a clinical trial for a genetic disorder. Now think back to 1974 (or imagine it, if you’re under 35 J). Back then, genetics was little more than a minor medical sub-specialty, diagnosing diseases few had heard of, and with little hope for treatments or cures.

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The Greenwood Genetic Center (GGC) opened its doors in 1974,under the leadership of two visionary co-founders, Roger Stevenson, MD and Hal Taylor, PhD, and with two guiding principles – offer the best most compassionate care and provide state-of-the-art technology. GGC began with support from the South Carolina Department of Disabilities and Special Needs, who in 1974 had the vision that in order to prevent or treat disabilities, they must be understood. They realized, even back then, that genetics was going to provide that understanding.

Now, 43 years later, GGC still operates under those founding principles of compassion and innovation, and we still ardently work to diagnose patients with both ultra-rare and common complex disorders, but what has changed are the dramatic advances in the field of genetics led by our scientists and colleagues around the world.

Hundreds of patients each year are served by our metabolic genetics treatment program, offering proven therapies to treat or prevent serious disabilities and health issues.

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Every single year, seventy babies in South Carolina are born free of birth defects of the brain and spine thanks to GGC’s Birth Defect Prevention Program.

GGC’s commitment to providing hope for families impacted by genetic disorders has led to the creation of the Center for Translational Research, which is leading the way in developing clinical trials.

Researchers at GGC are working to fundamentally transform the diagnosis of autism with the development of a blood-based test and work toward treatment trials.

GGC’s Division of Education provides outreach genetic education to students from middle school through post-graduate training, encouraging students to pursue careers in the sought-after and highly rewarding field of medical genetics.

In 1974, few people would have imagined the fundamental changes in medicine that would occur thanks to the field of genetics. Dr. Stevenson and Dr. Taylor imagined it. The South Carolina Department of Disabilities and Special Needs imagined it. And because of them, two generations have now benefitted from compassionate clinical care, enhanced diagnostic testing, cutting-edge research, and innovative educational programs.

The Gene Scene will share the stories of families, scientists, and innovations that have made these past 43 years so exciting, so rewarding, and so impactful, and are making the future so promising. Welcome to The Gene Scene.

Communicating Without Words

Mommy.  Daddy.  I love you.

One of the joys of parenthood is hearing your child say these words and phrases for the first time.  Toddlers and teenagers alike are notorious for having their own opinions and preferences.  Being able to share these thoughts and control some parts of their world is an important step in child development.

But what do parents do when their child isn’t able to talk?  When sign language isn’t an option?

Rett syndrome awareness month

Rett syndrome, and other similar neurodevelopmental disorders, robs individuals of the ability to communicate.  When verbal communication is no longer an option, families develop incredible means to communicate.  Spend time with a family of a girl with Rett syndrome, and you will witness the incredible bond between parent and child.  Parents can tell you which look means “I’m hungry,” which sigh says “I’m bored,” which laugh says “This is so much fun,” and which glance is a request for a favorite movie.  The love and trust that a child feels for a parent or sibling shines through without speaking.  Excitement over a new toy or skill is palpable.  Just as parents of infants can interpret a cry, parents of older nonverbal children learn what different sounds and expressions mean.  As one mom shared, “The instinct just grows.”

Devices have been developed to improve communication for those who are nonverbal.

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Rettsyndrome.org

Called augmentative communication devices, these can be as simple as a cards with the words “yes” and “no” to as complex as a computer that can track eye movements.  These options have obviously been a positive step forward.  Amazingly, some parents and families have developed their systems that can be quite complex and attempt to give their family member the ability to communicate more complex ideas.  As wonderful as these systems and devices can be, there are parents who say that their daughters connect with them better than devices.  Additionally, communication on the go is faster and easier without carrying around pictures or computers.

As incredible as this unspoken communication may be, parents of children with Rett syndrome continue to fight for their daughters.  Augmentative communication devices, medication to ease seizures and breathing irregularities, speech therapy, and, most importantly, a CURE.  These families continue to fight.  Fight for the awareness that being nonverbal doesn’t mean that you can’t understand what is being said to or around you.  Fight for their daughter’s right to advance in school and prove her ability to learn.

October is Rett syndrome Awareness Month. 

Previous social media campaigns have been built around #notspeaking and #LOUD to highlight the difficulties of those who are nonverbal.  Advocates for Rett syndrome continue to use their voices for those who can’t.  Maybe you can too.  And we can all work together for the day that a girl with Rett syndrome can say “I love you” out loud. You can learn more by visiting www.rettsyndrome.org.

“There are some people who could hear you speak a thousand words and still not understand you.  And there are others who will understand without you even speaking a word.”—Yasmin Mogahed

Lauren Baggett, MS, CGC
Genetic Counselor

October is Rett Syndrome Awareness Month

October is Rett Syndrome Awareness Month.

Rett Awareness Month SCThanks to Gov. Henry McMaster, SC is officially joining with the Rett syndrome community in honoring those families who face these challenges every month of the year. Join with us in supporting families like the Gunns, whose story is below. Learn a little about Rett syndrome and be a part of advancing research toward a cure!

Makayla was diagnosed with Rett Syndrome in April of 2015 at the age of two.  

At about 18 months, we noticed she had started some repetitive hand motions, and her pediatrician was a little concerned that she did not have many words.  She had learned some sign language, and was saying ‘mama’ and ‘dada’, but that was it.  Then she suddenly stopped all of that.  At her 2 year old check-up, the pediatrician referred us to BabyNet, SC’s early intervention program. Our BabyNet caseworker recommended that she be evaluated by the Greenwood Genetic Center.

We met with Dr. Mike Lyons at GGC’s North Charleston office. He evaluated Makayla and suggested some genetic testing. A few weeks later, he broke the difficult news of Makalya’s diagnosis in a most gracious way.  He also immediately recommended we meet with Dr. Steve Skinner in the Greenwood office, who is an expert in Rett syndrome. Though we were overwhelmed at all we needed to know, Dr. Skinner, Fran Annese, and the whole staff were wonderful at that first meeting, giving us all the time we needed to ask questions.  Their compassion for families like ours really showed through that day and continues to this day.  They have remained accessible and informative, staying up to date on any changes or developments related to Rett syndrome and sharing those as appropriate. They have been so encouraging for our family as we navigate through what, for us, are uncharted and scary waters.  We have also enrolled in the Rett Syndrome Natural History Study through GGC.

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But, Rett Syndrome does not define Makayla.

Despite her diagnosis of Rett syndrome, Makayla is a happy little girl.  We are blessed that she can do the things she can do!  She can still walk, unlike so many girls with Rett syndrome, but she also skips and runs in short distances when she is excited.  She loves being outside, and her favorite thing to do is play in water, at the pool, the beach, and even in the bathtub.  Close behind that is riding her rocking horse, which she would stay on for hours if we let her.

She also loves to watch sports, particularly basketball and football.  With four older brothers, she has had many opportunities to watch games!  And, she loves to dance, especially to Michael Jackson and Johnny Cash!

Makayla’s diagnosis has been an incredible challenge for our family, but learning about and dealing with Makayla’s condition has done a couple of amazing things.  First, it has drawn us closer together as a family.  Second, it has brought out a love in each of us that we just did not know was there.  I do not think there is any sweeter sound than when Makayla gets tickled and laughs and laughs.  Our boys at times even vie for a turn at holding her, and often we have to kick them out of her room at bedtime!  She has and continues to bless our family in so many ways.

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To learn more about Rett syndrome visit rettsyndrome.org

Hollis and Julie Gunn
Mt. Pleasant, SC

Not just the ‘PKU test’ anymore!

Not just the ‘PKU test’ anymore!NBS Awareness Month

Many healthcare providers still refer to newborn screening as “the PKU test”, since PKU (phenylketonuria) was the first and only condition screened for beginning in 1965. Thanks to the development of the blood spot card in 1963 by Dr. Robert Guthrie , all babies have a few drops of blood taken from their heel shortly after birth. We started out by looking for only PKU, and in the past 50 years, countless individuals with PKU have been identified and started on treatment – treatment that has prevented intellectual disability, seizures, and growth problems, and that’s amazing!

But newborn screening didn’t stop there!

Today’s test is so much more thanks to a combination of new technologies and new treatments. Technology has rapidly advanced in the 50-plus years of the newborn screening era, allowing us to detect many more disorders. A lot gets done with those few drops of blood – metabolic testing, hemoglobin testing, and more. Testing for some of the newest additions to the newborn screen, lysosomal storage disorders, only requires a tiny fraction of the blood collected from each baby, but requires new, high-tech instruments in the laboratory. Newborn screening now goes even beyond the blood test with non-invasive equipment used to check hearing and pulse oxygen (to identify heart disease).

Thankfully, along with advances in diagnosing these conditions, progress is also being made in the development of effective treatments.

The original treatment for PKU was (and still is) dietary management. With the right advice from geneticists and metabolic dietitians and a lot of careful attention to food intake from the family, the adverse effects of PKU can be avoided. This is not extraordinarily high-tech, but is very effective .

NBS Awareness Month

Many other conditions detected by newborn screening can be managed with diet and supplements or with a single medication (like thyroid hormone replacement for patients with congenital hypothyroidism). Patients with hearing loss identified at birth may benefit from the early use of hearing aids or cochlear implants, leading to not only better hearing, but also improved development and speech. Congenital heart defects that may have gone undetected for months, or even years, can often be surgically corrected right away. Other disorders, like cystic fibrosis and sickle cell disease don’t have a single treatment yet, but do have improved outcomes with early detection and comprehensive medical care.

For some of the most recent additions to our newborn screening panel, patients are unable to make a needed enzyme, so novel treatments like enzyme replacement therapy (replacing the missing enzyme with a medication) or bone marrow transplant (introducing healthy cells that can make the missing enzyme) are improving symptoms and quality of life.  Advancing technology has made these medications and procedures available and they can be life-saving for patients with these rare diseases.

So, how did we get to the 50+ conditions that South Carolina currently screens?

Each state determines which conditions are on their newborn screen, but all states now try to follow the national Recommended Uniform Screening Panel (RUSP)  of 34 core conditions and 26 secondary conditions. Anyone can nominate a condition for the RUSP, and often this is a combination of parents/advocates and researchers. Conditions are added to the RUSP after a committee reviews the scientific knowledge about the condition and the screening test. The reviewers are looking for an overall benefit of screening and whether it can be practically implemented, including things like:

  1. The condition is a serious health issue
  2. Enough is known about the rare disorder to be certain about the diagnosis
  3. An effective treatment exists
  4. Screening can provide quick results
  5. States can provide the screening with reasonable expenses
  6. Most or all babies with the condition will be detected, without too many false-positive results

Not all conditions will be approved, but as we continue to better understand how these conditions can be diagnosed and treated, the list is sure to keep growing. For example, Pompe disease was initially declined because of a few pieces of lacking evidence, but about 5 years later it was added to the RUSP. Soon newborns in South Carolina will be screened for this condition and given the chance to receive early treatment with a synthetic enzyme that will improve survival and quality of life.

Where are we going from here?

As new testing methodologies and treatment options become available, more and more conditions will be recommended and approved for newborn screening. It is truly an exciting time to be in genetics, as we are in the midst of amazing research and discoveries that are not only treating patients after symptoms develop, but with early detection, can prevent children and their families from the devastating effects of many of these conditions.

Dr. Guthrie likely couldn’t dream of the number of lives his innovation would save! The ‘PKU test’ has come a long way, and we are excited to see how families will continue to benefit as progress continues.

Jennifer Stallworth, MS, CGC

Saving 5,000 babies each year

5,000 babies.  That’s a lot of babies. 

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That is the approximate number of babies born each year with a condition detectable by newborn screening in the US.  This means that thousands of newborns are identified and able to receive treatment preventing permanent health and developmental damage.  In some cases, these treatments save the baby’s life before they ever even have a symptom.  I don’t know about you, but I think that’s pretty impressive.

While many new parents may be aware that their baby gets a little heel stick before they are sent home from the hospital, most probably do not realize the full extent of what goes on behind the scenes once that dried blood spot card is collected and what it could mean for their baby’s health.  Given that it is probably one of the most successful public health initiatives of all time screening millions of babies over the last 54 years of its existence, newborn screening tends to fly under the radar as an unsung hero in healthcare.

September is Newborn Screening Awareness month!

So we want to take this opportunity to share some facts about newborn screening, acknowledge the teams of healthcare providers and laboratories that make these programs possible, and let some of the amazing parents we work with at the Greenwood Genetic Center share their story with you.  Read on below for more info and stay tuned for the rest of the month for more posts!

Let’s start with some basic facts.

What is newborn screening? How is it done? And, what conditions are included?

Each baby born in the US is required by law to have newborn screening.  For most babies, this means they get a heel stick after the first 24 hours of life before they are sent home from the hospital.   Several drops of blood are collected on a filter paper card and then sent to a state lab for testing. In addition to the blood test, newborn screening also includes a hearing screen in all states and pulse oximetry (to screen for heart defects) in some states.  Each state in the US runs its own newborn screening program, so the number of conditions included and the process for the screening varies from state to state.  The Recommended Uniform Screening Panel, or “RUSP”, is a list of 34 core conditions recommended on a national level to provide some guidance and consistency among the individual state programs.  Most states screen for at least these 34 core conditions, but some states elect to screen for more and may include closer to 60 conditions.

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How do you decide which conditions to test?

In order for a condition to make it on the list for newborn screening, it has to meet some criteria first. These include:

  • A “good” screening test for that condition exists. “Good” means that the test is sensitive and specific enough to pick up all babies with the disorder without too many false positives. It must also fit somewhat within the current structure and methods of newborn screening and be cost effective since millions of babies will be screened every year.
  • An effective treatment is available for the condition.
  • There is evidence to support the benefit of screening babies at birth before any symptoms may be present. This means that by identifying these babies right after birth and starting treatment early, future health complications or cognitive impairment can be lessened or prevented altogether before any symptoms are even present.  Without newborn screening, these babies wouldn’t be diagnosed until much later when symptoms develop and by then, irreversible damage will have already occurred.

So, how does GGC figure into all of this?

In South Carolina, the Greenwood Genetic Center (GGC) has a long standing relationship with the Department of Health and Environmental Control’s (DHEC’s) SC Newborn Screening Program. The Center follows-up on screening results that are abnormal for one of the inherited metabolic or genetic conditions included on the panel.  This is where the GGC’s Clinical Metabolic Team comes in.  The team includes metabolic geneticists, a genetic counselor, dietitians, a psychologist, and clinic coordinators.  Initially, they consult with the pediatricians and recommend any additional testing. Once the diagnosis is confirmed, the metabolic team will follow that child on a regular basis.  They educate the family about the diagnosis and counsel them on the recurrence risk. They initiate and manage a treatment plan as well as help the family navigate other medical and developmental needs related to their diagnosis.

The GGC Diagnostic Laboratory performs much of the follow-up testing for these abnormal screens as well as the tests used to monitor the effectiveness of the treatment or diet.  The tests that are done as part of the NBS follow-up process have some of the fastest turnaround times of any of our tests in the lab.  Getting an answer fast is critical for these babies so treatment can begin as soon as possible.  This experience and expertise has allowed the GGC Diagnostic Lab to expand outside of South Carolina.  The lab now also works with a few other states in providing follow-up testing for some of the lysosomal storage disorders recently added to the NBS programs in other states and hopes to continue to grow these services.

We are proud of our metabolic clinical team and the diagnostic lab contributions to newborn screening in South Carolina and look forward to sharing more with you throughout the month!

Hope for Harper

Families are never fully prepared to learn that their beloved baby has a birth defect, but one SC mom is working to make their road a little less rocky by sharing her own story and advocating for the littlest patients.

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Travis Dew Photography

Stephen and Jenna Brown of Hanahan, SC were eagerly anticipating the birth of their first child, Harper. They found out she was a girl at a 15 week ultrasound and had seen her beautiful face at a keepsake 17 week scan. Feeling excited and confident, Jenna went alone to her doctor’s office for her routine 18 week ultrasound.  Though Stephen offered to come, Jenna had resisted, wanting him to go to work and have more time off when the baby arrived.

“When the doctor came in, the ultrasound tech reached out and took my hand. That was my first sinking moment of despair,” shared Jenna.

There was a cyst at the bottom of Harper’s spine, possibly spina bifida.

‘My daughter will never walk,’ was her first thought. As she waited in the office holding her daughter’s ultrasound picture and crying, Jenna texted her husband. Later that day they were worked in at the Medical University of SC (MUSC).

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Spina bifida was confirmed.

The Browns elected to pursue in-utero surgery which could provide Harper with the best hope for a positive outcome. After an amniocentesis and two long weeks of waiting, they drove to Philadelphia where the highly-specialized surgery is performed, ready to put their life on hold for baby Harper. Jenna endured 12 hours of testing only to learn that she was not a candidate for the procedure.

“We left Philadelphia devastated,” she said. “They reevaluated us at 25 weeks, but we still were not eligible for the surgery.”
At that point, the Browns met with Dr. Ramin Eskandari, a pediatric neurosurgeon at MUSC, to discuss Harper’s surgery after delivery. “He was the first one who gave us hope,” said Jenna. “This was not the worst-case scenario we had read about on the internet, maybe her lesion was even covered!”  When spina bifida lesions are covered they are protected from the damaging effects of the amniotic fluid.

The Browns followed up at MUSC every two weeks until Harper was delivered on June 17, 2015, with family in the waiting room wearing their ‘Hope for Harper’ t-shirts.

After delivery, Harper was whisked away for an evaluation, and Stephen went with her. “He came back to my room with tears flowing, but couldn’t get the words out.”

 

My heart sank again, but he said ‘No, it’s good – it’s covered.’

 

The next day Harper had her closure surgery. She went home on June 24th, her original due date.

Jane Dean of GGC’s SC Birth Defects Prevention Program met the family when Harper was about a month old. “I immediately fell in love with this strong, amazing family.”  Dean provided counseling and information and enrolled the family into GGC’s folic acid study.

“I was taking folic acid during my pregnancy,” shared Jenna, “so I wanted to help understand what other factors may be involved – why it didn’t work for Harper.”

Since Harper’s birth, Jenna has left her teaching career to become a full-time mom. Harper is thriving. She is walking and running thanks to successful surgeries and ongoing physical and occupational therapy. Now, Jenna and Harper spend their days volunteering with MUSC’s Children’s Hospital, hosting events, advocating for patients, and attending appointments with families who are facing the same challenges they have endured – providing hope.

NTD Jenna Brown

Jenna also recently joined Dean at a bridal show in Charleston to help promote the importance of folic acid before and during pregnancy.

“Your story could be different, your journey could be different than what you planned,” said Jenna. “Ours is, but there is always hope.”

Why haven’t we fixed this yet?

Why haven’t we fixed this yet?

Fragile X syndrome is the most common inherited form of intellectual disability. Approximately 1/4,000 males and 1/8,000 of females are impacted by this disorder which causes distinctive physical characteristics including a triangular-shaped face, large ears, a prominent chin, and broad forehead. Individuals with Fragile X also experience significant developmental delays, varying degrees of intellectual disability and autistic-like behaviors.

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By Peter Saxon (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons
The genetic cause for Fragile X syndrome was identified in 1991, during the early years of the Human Genome Project. The Fragile X syndrome gene, FMR1, is located on the X chromosome. Females have two copies of the X chromosome, while males have only one. This is why males are more frequently and severely affected by Fragile X syndrome. When the FMR1 gene is mutated, it is unable to produce a protein that is vital for healthy brain development.

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In the 26 years since the genetic cause was found, rapid progress has been made, including understanding of the pathophysiology of the condition, the development of animal models, and the identification of drugs that correct the features of Fragile X in mouse models.

This relatively rapid progress caused great excitement among the Fragile X community, and numerous clinical trials have been implemented in the past decade – nearly all have failed, showing no improvement.

But if we’ve learned so much about Fragile X, why haven’t we made more progress in treating it?

A new study recently published in the Journal of Neurodevelopmental Disorders offers a theory.

Walter Kaufmann, MD, the senior author of the study, says much of it has to do with how we are measuring the impact of the drugs.

In a review of 22 clinical trials that have been conducted on individuals with Fragile X syndrome, Kaufmann and his coauthors found that the trials failed in part because of the deficiencies of the outcome measures.

Outcome measures are the ways that researchers evaluate whether or not the study drug is having an effect. They can include self-report measures such as behavioral questionnaires, performance-based measures such as IQ tests, or even physiological measures such as biomarkers in the blood that may change with treatment. Outcome measures are compared before, during and after the clinical trial to assess the efficacy or impact of the drug.

“Part of the problem with these trials is that the tools that are being used to measure the drugs’ effectiveness are of limited or moderate quality,” said Kaufmann. “Many of the current outcome measures being used to assess cognitive improvement and behavioral changes in response to the drugs have not been proven to have reliability, validity or sensitivity to treatment.”

“These drugs may have had a benefit to the patient, but if we’re not able to measure that within the context and timeframe of the study, it is considered a failure,” he said. “And without concrete evidence to show efficacy, the trials are halted or never progress to the next level.”

Another shortcoming of the measures is that many are intended for long-term assessment, rather that the relatively short duration of most clinical trials.

If scientists can’t objectively and consistently show that a drug is having a meaningful impact on function and quality of life, the NIH and FDA will not move these trials forward toward an effective treatment, Kaufmann said.

“Measures for Fragile X syndrome were evaluated for this study because of the numerous clinical trials already done for this disorder,” said Kaufmann, “but the same issues exist for other neurodevelopmental disorders, including autism.  We must be able to quantitatively demonstrate therapeutic efficacy for these complex disorders. That is the key to success.”

What are we doing about it?

Since joining GGC in 2015, Kaufmann and his team have been committed to advancing clinical trials for neurodevelopmental disorders, including Fragile X syndrome, Rett syndrome, and autism. A key goal of GGC’s Center for Translational Research, which is headed by Kaufmann, has been to develop effective outcome measures for these disorders including scales, questionnaires, and biomarkers.

Dr. Walter Kaufmann is the Ravenel Boykin Curry Chair in Genetic Therapeutics and Director of the Center for Translational Research (CTR) in the Greenwood Genetic Center. Coauthors on this study include researchers from Johns Hopkins University School of Medicine, Rush University, Cincinnati Children’s Hospital, Stanford University, University of California Davis, and Novartis Pharmaceuticals

 

So You Want to Become a Genetic Counselor?

How did I get there?

I have been asked many times over the years how I became interested in genetic counseling. For me, the lightbulb moment came while I was in high school.  Early on, I had thought about several different future careers, including something in the healthcare field, but then I developed a special interest in genetics during my second year of biology and decided that I wanted to pursue some type of career in this field.

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I started looking at colleges that offered genetics as a major, and it all clicked one day as I was visiting my future alma mater.  While touring the school, I had the opportunity to meet with a professor in the Genetics Department, and he shared a booklet with me that described many different careers one could pursue with a genetics degree, one being genetic counseling.

As I read through this information, I learned that:

a genetic counselor is a health care professional who works closely with individuals who are undergoing evaluation and testing because there is concern for a possible underlying genetic condition, and they help to provide education and support to these individuals and their families during this process.

 

I was intrigued that genetic counselors could work with a variety of patients, including pediatric and adult patients, and they could practice in both the clinical and research settings.  I quickly realized that genetic counseling would be the perfect fit for me given my affinity for genetics and my interest in working in healthcare.  The rest, as they say, is history.

 

Well, there were actually a few more steps in there.

 

To practice as a genetic counselor, one must complete a Master’s training program.  Most genetic counselors enter their training program with an undergraduate degree in a biological science and/or psychology.  There are currently 37 accredited Master’s training programs in the US and several outside the US. Most programs have a two year curriculum along with a thesis requirement. The second year of the program is typically spent in clinical rotations where the student gains experience in seeing patients while being supervised by certified genetic counselors.  Once in practice, most employers require that a genetic counselor pass the board certification exam administered by the American Board of Genetic Counselors and maintain certification through completion of continuing education.

 

Because admission to a genetic counseling Master’s program can be competitive, I always encourage interested students to investigate several different programs to ensure they understand all of the prerequisites and suggest that they consider applying to multiple schools. Observation with a genetic counselor and volunteer work in a related area are also very helpful experiences when applying to graduate schools for genetic counseling.  The Greenwood Genetic Center offers a summer internship program in which undergraduate students can spend time in one of our clinical settings and learn about the field of genetic counseling. I was very fortunate to have this opportunity when I was in college and can say that this experience not only helped reinforce my decision to become a genetic counselor, it was also invaluable to me as I prepared to apply to graduate schools.

 

How can I learn more?

If you have interest in the genetic counseling profession, please reach out to a genetic counselor in your local area to learn more about opportunities that may be available for shadowing and observation.  We are happy to share our stories and answer your questions. You can find a local genetic counselor along with a wealth of other information at the National Society of Genetic Counselors’ website. The American Board of Genetic Counseling also has great information about the profession and Master’s training programs.

 

Good luck!

Brooke Smith

A Medical Mystery Revealed – a New Syndrome

“I was born almost like everyone else, but without knowing there was a small flaw in my genetics,” shared Daniel, 44. “At home, I was always treated as a normal person, a child like everyone else. It was not until the fifth year in school that I began to be a victim of bullying. This was like a kind of tunnel in my life, the years went by, and I even lost three years of high school because I did not know how to handle these emotions.”

ectrodactylyDaniel grew up alongside his family in Honduras suffering with a variety of internal medical issues including headaches and digestive problems. But it was the outward effects, including his unusual facial features that made life even more painful. Although he has dealt with the obvious effects of his condition all his life, no one had been able to identify what was causing it. Throughout his struggles, support from his family, friends, and faith helped him to persevere until they could find a solution.

Enter the Greenwood Genetic Center. Through the Center’s prior connection with medical professionals in Honduras, Daniel’s blood sample was sent to GGC for microarray analysis, to help identify the cause of his condition.

A microarray test (CytoScan HD) allows scientists to scan millions of areas of the genomes at the same time, looking for missing or extra sections. It is one of the first tests ordered on many patients and can be exceptionally helpful in unsolved cases like Daniel’s. Interestingly, Daniel’s microarray results revealed a known deletion involving chromosome 7, a deletion that causes a defect called ectrodactyly or split hand/foot malformation.

Funny thing is, Daniel didn’t have ectrodactly.

Ectrodactyly interrupts the development of the hands and/or feet. This deficiency can result in the absence of one or more of the central digits, causing them to take on a U or V shape. Sometimes digits which remain can be webbed.

Of the eight families known to have this particular deletion, only three individuals didn’t have ectrodactyly, or for that matter, any other physical issues.

So why was Daniel so affected, and in such an unexpected way?

Although Daniel didn’t have ectrodactyly, he did exhibit many other symptoms including facial abnormalities, heart problems, a spine deformity, hernias, and paranoid personality disorder. It was unprecedented for these symptoms to be present with this deletion, but without ectrodactyly. No one had ever thought to look for such a deletion before.

Even though the origin of his symptoms had been discovered, Daniel’s condition still did not match anything on record. So, in order to better diagnose patients in the future, a new name for this condition was created, Ramos–Martínez syndrome.

Though Daniel still faces struggles due to his disorder, his new knowledge that came with genetic testing has immensely improved his life. “Now I see a little more clearly and know myself much better,” he says. “I have a vital strength; I like to walk a lot, observe life, and think that even though I am not much different from what I was before starting the genetic test now I have a greater awareness of my life.”

Prior to his experience with GGC, Daniel poetically shared that he had “wandered like the people of Israel for 44 years … Like a gypsy, I went from doctor to doctor” with no one being able to properly diagnose him. Despite his turmoil, Daniel remained remarkably hopeful. “It is possible to be happy; even within my syndrome; happiness is you,” he wrote.

The Greenwood Genetic Center has made a profound impact in Honduras, a nation with few resources. For over a decade, the Center has been working in cooperation with medical professionals in Honduras, providing expertise, genetic testing, medications, and education for health care providers and patients in the impoverished nation. This relationship was started by Dr. Ken Holden, Senior Clinical Research Neurologist at GGC in Charleston, and continued by Dr. Steve Skinner through years of medical mission trips.

Recently, GGC’s Director of Research, Dr. Charles Schwartz, was invited to lecture on intellectual disability and birth defects at a Honduran medical school. It was on that trip that he met Daniel, a patient previously only known to GGC through a blood sample.

Addy Orcutt

 

Low protein diets in a high protein world- Part 2

PART 2

Last week you learned how our metabolic patients are diagnosed and how their low protein diets are managed during infancy.

But what happens when they start solid food?

There are very few foods that are truly protein free.  You may think of fruits as protein free, however, they do have a small amount of protein.  There is protein in all vegetables as well, although some are higher than others.  Any grain based foods will also contain protein in some amount including rice, pasta, crackers, and bread.  Nuts, beans, legumes and products made with these foods are higher typically in protein than fruits and vegetables.  And of course, all animal based products including dairy items are very high in protein.  There are very few patients with protein based metabolic disorders that are allowed to have any animal product, including eggs, cheese, yogurt, ice cream or even pudding.

The base diet for these patients is focused on fruits and vegetables.  Even with foods that are lower in protein, they still need to be weighed and calculated.  The gram scale doesn’t get put away once they are a toddler.  As a child transitions off of breastmilk or formula, they will remain on metabolic formula to supplement their diet.

Think about the nutrients found in higher protein foods – iron in meat, calcium and Vitamin D in dairy, healthy fats in nuts, fiber and vitamins in beans.  If you aren’t getting those in your diet, where are they going to come from?  There are many options as children age to help maximize the supplementation of their diet with different metabolic formulas.  But they will remain on some type of formula for supplementation throughout their life.

Remember that patient with PAH deficiency?

Woman eating salad

They have done well through their infancy, levels have been maintained, they like their formula and the caregivers are excited to transition to table foods and get them off of infant formula.

We initiate solid foods as we would with any child, starting around 5-6 months old with cereal and baby foods.  The only difference is that the cereal and baby foods are weighed and provide a specific amount of phenylalanine.  The metabolic formula is adjusted to supplement the diet and provide the additional nutrients to maintain growth and development.

The caregivers become very proficient in math, calculating out daily menus that provide specific amounts of phenylalanine at every meal and snack through the day.  If a child doesn’t finish their breakfast, the amount of phe not eaten has to be added into the next snack or meal so that at the end of the day, they full amount is received.  If they leave a little or get a little extra, it usually isn’t a problem every once in a while.

The problems arise when they get too much on a daily basis and their levels are too high, or they get too little on a daily basis and they have slowed growth and development.

Communication between the team and the caregivers remains very important! 

For some of the protein disorders, the protein calculation must be even more exact, and serious complications can arise very quickly if those needs are not met.  Some of those patients go through their life with a feeding tube so that their treatment needs can be met during illness or even when they are being a typical stubborn toddler who doesn’t want to eat.  Getting too much or too little is not safe for those disorders and must be dealt with immediately with changes to their treatment plan and formula.

Yeah, but what about as they get older?

Things continue to get more complicated as a child ages.  The amount of food a 2 year old wants to eat in a day vastly changes by the time they are 10 or 12 or 16 years old.  For instance, we’ll say our patient is allowed 275 milligrams of phe a day (or 5 ½ grams of protein).  The caregiver splits this up between 3 meals and 3 snacks.  A typical breakfast for this patient provides about 25 milligrams of phenylalanine.  So our 2 year old eats 2 tablespoons of Froot Loops and 2 tablespoons of cantaloupe along with their metabolic formula.

Not too bad!  But now that 2 year old is a 12 year old who still only gets the same amount of cereal and fruit.  They are probably going to be hungry fairly soon!  How do the caregivers, and the patients, work around this?  One thing that does help is the development of specialized low protein foods that are made for metabolic disorders.  There are many options including low protein pasta, rice, bread, meat substitutes and cheese alternatives.  These foods are not sold in the store however, they must be ordered online.

And they are fairly expensive.  Here is a comparison between “regular” foods in the grocery store and the low protein equivalent that families have to order –

Regular

16 oz elbow macaroni = $1.79

16 oz box spaghetti = $1.00

2 pound flour = $1.99

White bread (18 slices) = $0.99

Chips Ahoy cookies = $3.00

8 oz shredded cheddar = $3.79

24 count American slices = $4.49

Total = $17.05

Low Protein

16 oz elbow macaroni = $13.98

16 oz box spaghetti = $9.99

2 pound “baking mix” = $13.33

White bread (18 slices) = $14.61

Sugar cookies = $13.00

8 oz shredded cheddar = $6.33

24 count American slices = $9.37

Total = $80.61

Taco bar

The low protein foods are 4 times that of regular foods in the store!  These foods can be very cost prohibitive for most families.  But if they are able to get them, they can definitely change the amount of food at a meal or snack and help make a child’s daily intake much more acceptable.

Another thing that has helped our protein patients is the increase in gluten free foods.  Gluten is the wheat protein in food so when that is taken out, it decreases the protein in that food.  Some patients are allowed enough protein that gluten free foods, which are in most stores, are part of their diet.

Dairy alternatives also help.  For instance, almond milk is very low in protein – 1 gram of protein per cup versus regular milk at 8 grams per cup.  Many patients can use these types of products to have more options for dairy type foods including cheese, yogurt and ice cream.

How do the kids react?

While the calculating and mixing and measuring and meal planning is overwhelming enough, then factor in normal psychological and social development as a child ages.

The toddler may not mind that they have “special milk” or “their pasta” or that Mom mixes up a “special cheese” for them.  A 10 year old in school who has to go through the lunch line and gets handed a tray with “special” food may not feel the same way.  They may feel isolated from their friends who are grabbing slices of pizza or eating a cheeseburger.  They may not want to open up their thermos of metabolic formula because it smells funny and they are afraid people will laugh at them.  They may be upset that they are different and have a disorder that changes what they can eat or drink.

If you think of all the things that are influenced by, or influence, our diets, imagine that changing because you can’t eat like everyone.  Going to birthday parties is different because you have to take a dairy free, egg free low protein cupcake your Mom made and you can’t have the birthday cake everyone else is having.  Imagine going to camp and having to take your own cooler with formula and food because you can’t have what everyone else is having at lunch.  Even holidays with your own family are different because while everyone else is having turkey and stuffing, you are having a low protein pasta with vegetables.

Trips are hard because you have to make sure and take your metabolic formula, your gram scale, have your phe calculating app on your phone up to date and have food packed because you can’t just stop at a fast food restaurant for lunch.  The diet is for life, nothing changes the need for protein restriction, for formula supplementation, for having blood drawn and levels assessed.

Children, and adults, will rebel at formulas, sneak foods, stop checking levels.  These are normal compliance issues that happen with chronic disease.  When you live with something daily, it becomes too hard to deal with some days and that’s understandable.  We do our best to help our patients own their disease, to accept the steps needed for treatment and to embrace them.  We encourage talking with friends, telling people about their disorder, setting up a support system of friends and family that will give them the boost they need on a bad day.

There is nothing more heartwarming than having a patient tell you that their friends pick restaurants based on whether or not there will be low protein or vegetarian options so they can eat too!

This is just the tip of the iceberg when it comes to treating patients with metabolic conditions.  Hopefully though you will get an idea of the work and effort it takes the patients and their caregivers every day as well as how much we care for and support our patients.  This is an amazing group of patients to work with and the Metabolic Treatment Team takes their job to heart.  We enjoy seeing “our babies” grow into young children and adolescents and adults who have jobs and families of their own.

So think about protein the next time you sit down to a meal.  If you are really adventurous, try to go a whole day with only 5 or 6 grams of protein TOTAL.

You will see what our patients deal with daily and how important it is that we continue this work with metabolic conditions.  We can hope for enzyme replacement therapy or gene manipulation, but until that day is here, our families are living with this complicated treatment.

Having more people aware of these rare diseases and the effort needed for treatment will hopefully open the door for new and exciting advances in the years to come!

Amie Thompson