Cerebral Folate Deficiency
Tina Carkhuff, a director at Memorial Hermann Healthcare System, had a healthy two year-old son when she became pregnant again in 2004.
She and her husband Kyle were living near Philadelphia. They grew concerned when a prenatal screening revealed problems in-utero.
“First ultrasounds uncovered our baby had ventriculomegaly, a brain abnormality where the lateral ventricles measure larger than 10mm,”she says. The Carkhuffs were sent for further testing at The Children’s Hospital of Pennsylvania (CHOP).
With no definitive answers, they spent the remainder of the pregnancy worried, but hoping for the best.
Early Problems
Evan was born on September 22, 2005 and failed his newborn hearing test. There were other early problems as well.
Evan was unable to latch on for nursing and then had trouble with his sucking reflex when using a bottle. He was also small for his age and not growing normally.
“He was your typical floppy baby,” says Tina. “I kept going to our pediatrician wondering what was wrong. Finally, we were sent to a neurologist who ordered testing at CHOP.”
The testing was invasive and exhausting as they attempted to rule out various neurological disorders. Evan was started on daily injections to promote growth but tests did not reveal any specific cause for his delays.
He received ear tubes, and took part in physical, occupational and speech therapy. “Evan was 18 months, not walking, not talking, not making eye contact,” recalls Tina. Around this time, Tina started wondering if it was possible her son had autism.
Relocation to Houston, Texas
When a career opportunity made relocating to Houston possible, the Carkhuffs jumped atthe chance. “Our moving to Houston was related to the access to health care. We figured there were a lot of resources here,” says Kyle. The Carkhuffs hoped these resources would have some answers for Evan.
The team at Texas Children’s Hospital recommended repeating tests that had been done at CHOP. Tina was apprehensive about going down thesame road again.
“I just didn’t want to put him through that again,” she says. Instead, they took Evan to an autismclinic in Kingwood for evaluation. Evan was now two and a half years old and still not talking. He would not communicate with his family or teachers and was prone to constant tantrums. He also suffered from chronic diarrhea and insomnia.
Dr. Richard Frye, Pediatric Neurologist
The doctor at the clinic confirmed the autism diagnosis and recommended further treatment by Dr. Richard Frye, a pediatric neurologist atChildren’s Memorial Hermann Hospital.
By this time, Tina had joined Memorial Hermann Health System’s Information Systems department. She remembered reading a story in the employee newsletter about another child who was successfully treated by Dr. Frye’s clinic. Hoping for some answers, Tina took Evan to be evaluated.
Antibody Blood Test
“At the first appointment, Dr. Frye recommended more tests,” says Tina. “In addition to an MRI, he ordered blood work that would be sent to a lab at a university in New York. I did not understand what this test was for but Dr. Frye explained that we would need to send a check directly to an out of state lab since they did not take insurance.”
The test was to determine if Evan had an antibody that blocked the transport of folate, a B vitamin, from the blood stream across the blood-brain barrier into the nervous system. This antibody is one of the cause sof Cerebral Folate Deficiency, or CFD.
Diagnosis of Cerebral Folate Deficiency
Several months later, Dr. Frye confirmed Evan tested positive for the antibody and probably had CFD. He prescribed folate in the form of Leucovorin Calcium and told the Carkhuffs they could start seeing changes in as little as one week.
As promised, Evan’s transformation began. “Within one week, we saw something amazing!” says Tina. “Evan started to run.” Until this point, Evan walked with difficulty due to low muscle tone. His parents were thrilled by this change.
“The next week brought us even more surprises,” recalls Tina. One day she was in the pantry with Evan.Typically, he would reach for the item he wants, but that day was different.“Evan pointed to a box of cereal, turned to me and said, “Mommy, I want that!”
Evan had never addressed Tina as “mommy” before and this was also his first time speaking a full sentence.
Improvements in Language and Interactivity
After just five weeks of being treated for CFD, Evan’s language and interactivity changed so much he was no longer classified as autistic.
Dr. Frye told Tina and Kyle that Evan’s social skills had progressed to the point where he had outgrown that diagnosis. The Carkhuffs continue to see great progress.
“His behavior has settled down,” shares Tina “He used to throw fits or sit in front of the TV like a drone. Now he gives hugs and kisses, greets people at the door, and plays with his brother.” Now five years old, Evan also uses assisted technology tools, like the iPad, to learn and communicate.
A Link Between Autism and CFD
Dr. Frye remembers Evan’s early days of treatment well. “Evan was one of the first children I tested for the antibody,” says Dr. Frye. “Since then we have found the number of children with autism who are positive for the CFD antibody is astronomical.”
The disease was only discovered in 2005 and research is still in its infancy. “Another doctor and I recently reviewed our results on 77 children with autism, and according to our rates, about 63 percent of these children with autism also have the antibody associated with CFD.”
Having the antibody is only one part of the equation however, according to Dr. Frye.
“CFD is associated with other conditions such as mitochondrial disorders and children with CFD do not always have autism. The gold standard for diagnosing CFD is a spinal tap, which is an invasive procedure. At this point we are trying to determine if it is possible to use the antibody test and clinical characteristics to identify those children with CFD so they can undergo treatment without having to have an invasive procedure.”
The timing is pivotal. “Initial studies show that the earlier you treat it the better,”states Dr. Frye. “When we diagnose and treat kids older than five years old, there’s less recovery than children treated at two or three. That’s one reason that awareness campaigns among parents, educators and health care providers are important. Right now, too few people know about it.”
Continued Research
Dr. Frye says continued research is necessary. “The key is to determine which childrenmost likely have CFD so they can be identified and treated early. We need to perform further investigations to identify these children and document the response to treatment in a clinical trial setting.”
Fundraising for CFD
The Carkhuffs believe they have a duty to give other families the happy ending they are experiencing.
With the help of the Memorial Hermann Foundation, they are raising funds to support the ongoing research being done by the team at the University of Texas Health Science Center at Houston (UTHealth) Medical School and Children’s Memorial Hermann Hospital.
In addition, they hope to spread awareness to pediatricians and other doctors so more autistic children can be screened for CFD.
“The test costs just 100 dollars but it’s more than some families can afford,” says Kyle. “With the money we raise at least kids can get screened.”
As more children like Evan are being treated with folinic acid, the results are exciting.
“We are trying to show the high rate of positivity of the CFD antibody but also are trying to document that children with the CFD antibody really respond to this treatment,” says Dr. Frye. “Preliminary information from parents suggests that they see improvement in receptive language and attention.”
Kyle describes Evan’s transformation as someone whocame out of a fog into sunshine. “From where he’s been to now and it’s like we have a different child,” says Kyle. “It’s tremendous.”
For the Carkhuffs, diagnosing Evan’s CFD was the ultimate game-changer.
“We went to three hospitals and over 30 specialists before Dr. Frye and Children’s Memorial Hermann Hospital gave us our child back,” saysTina. “Dr. Frye offered hope we couldn’t find anywhere else. He took the time to listen and did not give up on Evan.”