From just a tiny sample of blood, a lab can test for 35 rare diseases in newborns that, if left undetected, could lead to seizures, developmental delays, permanent brain damage or death.
If results are positive for a metabolic disorder, these labs turn to the experts at CHOC Children’s metabolic laboratory for further analysis and treatment of newborns just days old.
September is Newborn Screening Awareness Month, and Dr. Jose Abdenur, director of CHOC’s metabolic laboratory, stresses the importance of these newborn screenings in order to prevent such grim scenarios from playing out.
Newborn screening is a public health program that screens all babies for many serious but treatable genetic disorders, and CHOC is one of the state’s largest referral centers for the program. All babies born in California are required to get screened soon after birth, but the diseases babies are screened for varies by state. In Orange County alone, some 38,000 babies are born every year.
CHOC is the only location on the West Coast for children who need cutting-edge treatment for certain metabolic diseases that can be detected from newborn screenings. Further, CHOC’s metabolics program is a leading destination for children from around the world afflicted with certain metabolic disorders, which are rare genetic disorders that result from a missing or defective enzyme in the body. These include disorders such as galactosemia, which impairs the body’s ability to process and produce energy from the sugar galactose, and adrenoleukodystrophy, which causes the buildup of very long-chain fatty acids in the brain.
“There are many, many very good success stories at CHOC, but there are still many things we can improve,” Abdenur says, citing too many false positives for some conditions that make families feel anxious and worried. “But we continue to get better at this.”
Newborn screening began in the 1980s. Over the decades, the Department of Health and Human Services has added recommended disorders for states to screen for in their newborn screening (NBS) programs. There now are 35 core conditions on the so-called Recommended Universal NBS Panel, as well as an additional 26 secondary conditions.
In addition to metabolic disorders, newborn screening can detect disorders related to hematology and immunology — such as sickle cell disease — as well as endocrine disorders, pulmonary diseases including cystic fibrosis, and such neurological conditions as spinal muscular atrophy.
Christine Schweer knew early on that her son, Colten, faced
some health complications.
Christine, a pediatric intensive care nurse living in the
Midwest with her husband, Todd, and then 3-year-old daughter, Chloe, recalls
feeling different during her pregnancy with Colten. Once Colten was born,
little things started popping up, she says.
Over the next few months, Colten developed several symptoms:
cold hands and feet, a sleepy demeanor, strange breathing and chronic, involuntary
eye movements – a condition called nystagmus.
At this point, Colten had already gone through several emergency department visits, including an admission to the hospital for respiratory syncytial virus (RSV) and eventually unexplained heart failure. But after genetic testing and screening for cystic fibrosis, cancer and blood clots all came back negative, Colten and his parents and doctors were left confused.
Searching for an answer
Colten was 6 months old when two new symptoms arose. An
occupational therapist thought Colten’s vision and hearing were waning, and an
ophthalmologist confirmed the therapist’s suspicion.
Then, around 9 months old, Colten’s weight mysteriously began
Meanwhile, the Schweers decided to relocate to California to
be near family. Christine, who now works in the PICU at CHOC Children’s at
Mission Hospital, transferred all of Colten’s records to CHOC. She began to
schedule visits to a team of CHOC providers, including pediatrician Dr. Lauren
Dwinell and pediatric cardiologist Dr. Anthony
Armed with her signature beach bag full of Colten’s records,
Christine continued the search for a diagnosis with Colten’s new care team, led
by Dr. Chang.
“We hit it off right away,” Christine says of Dr. Chang. “He
admired me for my dedication and advocacy for Colten, and I respected him for
his thoroughness, for trusting my parental instincts and for his commitment to
innovative treatment. We developed a good rapport and a lot of trust. He would
listen to me and recommend next steps for us both; then we would meet and
But the Schweers and Dr. Chang were still puzzled by
Colten’s symptoms, and Colten was now 2 years old.
“Nothing was adding up,” Christine says. Colten’s heart
function would worsen if off his medication, and his weight continued to climb.
“He was eating healthy and walking, swimming and exercising a lot, but his
weight was not budging.”
A few years passed while they continued to search for an answer.
An answer at last
Dr. Chang suggested they revisit genetic testing, despite
Colten having received genetic testing a few years prior.
“We trusted Dr. Chang’s instinct,” Christine says. “He
pointed out that tests can change even in a short time, and he wanted to be
sure we covered our bases.”
He sent them to Dr. Neda Zadeh,
a CHOC pediatric geneticist and Associate Director of the Molecular Diagnostic
A thorough walkthrough of Colten’s history and several
questions later, Dr. Zadeh had an idea. Recalling a case she encountered during
her fellowship at Stanford University, she brought up a rare condition called Alström
Syndrome and suggested they test for it.
While they waited, Christine got to work researching Alström Syndrome symptoms and immediately knew they had figured it out.
“Alström checked all the boxes: heart failure, flat and wide
feet, nystagmus, obesity and delayed developmental milestones – it completely
fit,” Christine says.
Six months later, a genetic sequencing test paid for by the foundation Alström Syndrome International confirmed what Christine and Dr. Zadeh suspected – Colten had Alström Syndrome. He was the 972nd person in the world to receive the rare diagnosis. By this point, he was 8 years old.
The Schweers were immediately welcomed into the Alström
family, Christine says. They got involved with the foundation that covered
Colten’s genetic testing, and families around the country and globe reached out
to them. Colten even met one of his current best friends, a boy with Alström
Despite the relief of a diagnosis after years of searching, Alström
came with some difficulties. The diagnosis meant that Colten’s vision was weak
and that his hearing would decline, too. The disease also affects his lungs,
kidneys, liver and weight.
“It of course felt horrible at first to me and my husband to
learn that Colten has a rare disease, but it was also a relief to know that we
had an answer now; there wouldn’t be so many surprises anymore,” Christine recalls.
The Schweers continued to work with Colten’s specialists, finally certain they knew the cause of his symptoms.
Collaboration is key
Christine reflects on the years of searching for answers and, despite the difficult moments, feels thankful for their collaborative care team at CHOC.
“If it weren’t for Dr. Chang suggesting more genetic
testing, if he hadn’t advised we see Dr. Zadeh and if it weren’t for the Alström
case Dr. Zadeh remembered from years before, we probably wouldn’t have figured
it out,” she says.
Christine thanks Dr. Chang for always keeping innovation in
“It would be easy to think inside the box and rely on past
test results,” Christine says, “but Dr. Chang always stayed up-to-date with
tests and looked at things creatively. It’s a multidisciplinary team approach
Most importantly, Christine admires the way Colten’s care
team relates with him.
“Doctors at CHOC are very personal with Colten,” she says.
“They get on his level and take time to get to know him and what he’s been up
to. Colten trusts them and wants to make them happy, so it’s always a positive
experience for him to see them.”
The approach has resulted in a fruitful partnership between Colten,
his parents and his providers.
“We’re all such a good team now. We feel confident we’re
doing everything we can possibly be doing for Colten.”
Learning about rare
disease at Peds2040
The experience getting Colten’s diagnosis sparked in
Christine a connection to the rare disease community. She heard about a rare
disease panel planned for the Pediatrics 2040
Conference, an annual conference on innovation in pediatrics spearheaded by
Dr. Chang, who had since been appointed CHOC’s Chief Innovation Officer and
head of CHOC’s Sharon
Disney Lund Medical Intelligence and Innovation Institute (MI3). Christine expressed
interest in attending right away, so MI3 sponsored her to attend. The
experience was invaluable.
“It was a great learning opportunity,” Christine says. “I
had lunch with a speaker whose son had a rare cancer, spoke with other families
and shared Colten’s story with providers, interns and residents.”
Thinking back to Colten’s journey to a diagnosis, Christine
felt grateful they had MI3 and Dr. Chang on their side. Peds2040 highlights the
importance of medical innovation to those with rare diseases.
One of the most memorable moments of the conference for Christine was Colten arriving toward the end of the day, when he was able to catch up with Dr. Chang.
Today, Colten is a loving, strong-willed, intelligent
13-year-old with a deep love of cars and an amazing memory. These days, he and
his family are grateful to be able to go several months between specialist
Even so, Christine notes, he faces some difficulties.
He is short for his age, so they’re seeing endocrinologist Dr. Himala Kashmiri to monitor his hormone levels. Additionally, like his vision, Colten’s hearing has waned and will continue to weaken during his teenage years. But, Christine reports, he has learned braille and thriving at it. And, because Alström can affect multiple organs, they continue to watch his heart, liver and kidney function with the help of medication and several specialists.
Colten continues to see Drs. Dwinell and Chang, along with nephrologist Dr. Shoba Narayan, pulmonologist Dr. Chana Chin, gastroenterologist Ellen Schoenfield, NP, registered dietitian Vanessa Chrisman, audiologist Dr. Kristi Panek and a pediatric ophthalmologist.
Nevertheless, the Schweers ensure Colten is empowered to do
what he wants.
“We’ve never held him back from doing something,” Christine
says. “If he wants to do something, we’re going to make it happen.”
Colten joined a Challenger baseball team for kids with
special needs, now one of his favorite activities.
And, despite vision loss, his love of cars is as strong as
“Before, he could instantly tell you what a car was when he
saw it” Christine says. “Now, he can identify them by sound.”
Some of Colten’s favorite memories so far include joining
his baseball team, going horseback riding and ziplining, and he has plenty more
“Despite his challenges, he’s very determined and has a
don’t-baby-me, I-can-do-this attitude that impresses me – and makes me a
nervous wreck,” Christine adds.
“When Colten was little, his doctors said he might not be able to talk. Now we joke that we have to beg him for five minutes of quiet. He doesn’t stop talking when he’s around his loved ones.”
Advice for other
Christine looks back at the difficult road to a diagnosis
and is now grateful for the community that Alström has brought her family.
“Let yourself grieve after a difficult diagnosis,” she says, “but also try to recognize you’re part of a new family. You’re not alone in this. Know that there are other parents out there who know what this feels like, so don’t try to take it on all by yourself. Despite how it can feel at first, every day is not going to be a bad day.”
As Thanksgiving approaches, CHOC Children’s physicians explain what they’ll consider when giving thanks this holiday.
“CHOC has provided me with lifelong blessings. I am grateful to have grown up at and with this hospital, from the initial CHOC Tower to the current Bill Holmes Tower, through pediatric residency training and beyond. To now be a member of such a remarkable team of providers — including our nurses and support staff — is both humbling and inspiring. Every day, I am especially thankful for the families who cross our threshold, and entrust the care of their most precious children to us. With continued commitment and dedication toward the health and well-being of our children, the future will be brighter than any of us can imagine.” – Dr. Neda Zadeh, genetics
“I am thankful to be working for an organization that creates an environment where our patients become our family. I am also grateful that CHOC Children’s has the foresight to invest in the innovative ideas we have to improve the health care we provide.” – Dr. Kenneth Grant, gastroenterology
“I am thankful for the opportunity with be partnered with an excellent children’s hospital. I am also thankful for the pleasure of working with other positive people who provide outstanding care to the children of Orange County. Together, we work to improve the care and services we deliver to our most important resource — our children.” – Dr. Daniel Mackey, pediatrics
“I am grateful for the incredible team we have in oncology, inlcuding doctors, nurse practitioners, physician assistants, nurses, the research team, members of ancillary services, our inpatient, clinic and OPI staff, administrative support, and other subspecialists, who all have great minds and compassionate hearts, and walk the difficult cancer journey with our patients and their families. I am humbled to be with such great company here at CHOC, who care deeply for children.” – Dr. Lilibeth Torno, oncology
“I am most grateful to the people behind the scenes at the hospital who do all the invisible jobs that are so important to keep CHOC Children’s running: the housekeepers, lab and x-ray technologists, bio-medical engineers, pharmacy technicians, scrub technicians, security guards and maintenance staff that work tirelessly, 24-hours a day.” – Dr. Gary Goodman, critical care
“I am most thankful for the ability to practice alongside of the caring and professional staff and physicians at CHOC, who all share the common goal of caring for children. Working together, we are able to tackle incredibly complex and varied problems that present in the amazingly diverse population of children that we serve.”
“I am thankful for so many things here at CHOC. I feel truly blessed every day to have found a professional community of like-minded caregivers who share a passion and dedication for continued improvement in the care we provide. I am also so grateful for the opportunity to meet and care for such incredibly courageous patients and to become a part of their families. Finally, I am thankful to my teams within the pulmonary division, the Cystic Fibrosis Center and the muscular dystrophy clinics for their selfless care of our patients. I wish our entire community a healthy and happy holiday season.” – Dr. Amy Harrison, pulmonology
“I’m thankful for the opportunity to serve my patients and families, and to help them secure bright futures through CHOC’s world-class care. I am also so grateful to work among a team that is steadfastly committed to the health and well-being of children in our community and beyond. “
With the number of children with complex medical needs expected to double in the next decade, an upcoming CHOC Children’s conference will provide important information for medical providers who are diagnosing and treating this patient population.
The conference is recommended for community pediatricians, family practice physicians, and internal medicine physicians, as well as a variety of specialists, including gastroenterologists, cardiologists, neurologists, rheumatologists and pain specialists.
“These are multisystemic disorders with a variety of symptoms. If patients and physicians are not aware of some of these underlying diagnoses, patients may be experiencing diagnostic odysseys for years prior to an actual diagnosis being made,” says Dr. Neda Zadeh, a CHOC geneticist who will moderate the conference. “Earlier diagnosis is always better.”
Following the conference, attendees will gain new skills related to these conditions:
Recognizing the symptoms for some of the more common connective tissue disorders including EDS and hypermobility type, and referring accordingly to appropriate subspecialty.
Understanding the symptoms for POTS and how to assess for this in the outpatient medical setting;
Recognizing features of mast cell activation disorder, and understanding how this relates to certain forms of EDS;
Improving knowledge of chronic pain and connective tissue conditions in children and adolescents;
Recognizing the signs and symptoms of a possible underlying connective tissue disorders, as well as the resources and referrals available; and
Improving knowledge and treatment of chronic pain in children and adolescents.
A complementary conference Dec. 3 and 4 is dedicated to teen patients with connective tissue disorders and their parents. If you have a patient who would benefit from the conference, they can also find registration information on CHOC’s website.
CHOC Children’s Neurofibromatosis Program – a recently nationally recognized program by the Children’s Tumor Foundation as a Neurofibromatosis Affiliate Clinic – provides comprehensive care to even the most rare medical issues in association with Neurofibromatosis type 1 (NF1).
NF1 is a common genetic condition that primarily affects the skin and the nervous system and is caused by a change or mutation in a single gene called NF1. This condition occurs in approximately one in every 3,000 children. The majority of these children do very well, have happy and healthy lives and may not have major skin issues, developmental disabilities or other neurological issues, says Dr. Neda Zadeh a CHOC medical geneticist and associate director of the Molecular Diagnostic Laboratory at Genetics Center. However, due to the known complications that can accompany this condition, comprehensive multidisciplinary care is strongly recommended.
“Half of the time, NF1 can occur for the first time in a child due to a spontaneous mutation in the NF1 gene at the time of conception, and is not inherited from a parent,” explains Dr. Zadeh. “It is important for parents to realize that this condition is not the result of anything an expectant mother did or did not do during her pregnancy. In the other 50 percent of patients, we often will see that one of the parents also has NF1 and may not even realize it.”
In order to meet criteria for an NF1 diagnosis, patients must meet two of the following criteria established in 1988 by the National Institutes of Health (NIH), summarized below:
Six or more café-au-lait macules of a specific measured diameter depending on the age of the individual (over 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals).
Two or more neurofibromas of any type or one plexiform neurofibroma.
Freckling in the axillary or inguinal regions.
Two or more iris Lisch nodules (iris hamartomas) observed on dilated eye exam.
A distinctive bony lesion (sphenoid dysplasia or tibial pseudarthrosis).
A first-degree relative (parent, sibling, or offspring) with a known diagnosis of NF1 as defined by the above criteria.
These NIH diagnostic criteria are extremely accurate in adults and children over the age of 5 years. A diagnosis of NF1 should be suspected in individuals who have any one of the above findings. Often if children are younger than 5 at the first evaluation, he or she may not yet have met the above criteria, but may do so after they reach school age. For this reason, visiting a geneticist on a regular basis is important in order to monitor and care for the patient. Also, in certain cases in which a diagnosis is not completely clear, or there is concern for a different diagnosis, genetic testing via sequencing and deletion/duplication analysis of the NF1 gene is available and usually coordinated after genetic counseling occurs.
Neurofibromatosis type 2 (NF2), a completely separate disorder, is even more rare than NF1. A patient with NF1 is not at an increased risk compared to the general population to have NF2, especially if there is a negative family history.
Children with NF1 require care from multiple specialists including neurosurgery, neurology, oncology and orthopaedics, and at CHOC is seen at least annually by a geneticist, who aids in coordinating care and management of the condition. CHOC’s multidisciplinary NF clinic involves all of the above specialists in the routine care of children with NF1 and other related disorders.
“We also can provide information to a patient and their families regarding the possibility to have further children in the family with NF1,” says Dr. Zadeh.
CHOC’s Neurofibromatosis Program has been treating children with NF1 for more than 30 years and annually cares for at least 150 children with NF1. The special program includes CHOC specialists currently involved in cutting edge clinical trials that are not available at many pediatric centers.