Hope Nicholas and Nathan
Patient Stories
When a disease has no single identifying feature and a variety of manifestations, diagnosis becomes complex.
The stories of children and adults with a mitochondrial disease are all different, but they have one thing in common.
Unless they’re lucky enough to find an astute diagnostician early in life or a specialist in mitochondrial disorders, their medical records are long histories of chronic health problems, repeated hospitalizations, partial or incorrect diagnoses and questions without answers.
Mitochondrial diseases result from failures of the mitochondria, specialized compartments present in every cell of the body except red blood cells. Mitochondria are responsible for more than 90 percent of the energy needed by the body to sustain life and support growth.
When they begin to fail, less and less energy is generated within each cell, ultimately leading to cell injury and in some cases, cell death. If the process is repeated throughout the body, entire systems begin to fail, compromising the life of the patient.
Often referred to as “mito,” the diseases most frequently affect the cells of the brain, eyes, ears, heart, liver, skeletal muscles, kidneys and the endocrine and respiratory systems. They produce a variety of symptoms, depending on the cells affected.
In addition to neurological issues like seizures, symptoms may include muscle weakness and pain, loss of motor control, gastrointestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, visual and auditory problems, developmental delays and susceptibility to infection.
Nicholas
Nicholas came into the world five weeks early with hyperbilirubinemia, a treatable condition that affects about 80 percent of premature babies. The high levels of bilirubin in his blood caused him to develop jaundice, a yellow discoloration of the skin and whites of the eyes. He was not eating well, which his caregivers attributed to the jaundice.
After two days in the neonatal intensive care unit (NICU), Nicholas went home with his parents. He was hospitalized soon after for five days of phototherapy to help his body eliminate the excess bilirubin.
“When he came home, he still wasn’t eating,” recalled his mother, Melody. “It took us an hour and a half to feed him. He was our first child, and it was a very stressful period for us. Both my husband and I got sick, and he got sick from us.”
Nicholas was hospitalized at the age of six weeks with respiratory syncytial virus (RSV), a common but challenging virus that accounts for 20 to 25 percent of pediatric hospital admissions nationally.
“Our doctor told us he was not eating because of the RSV,” Melody said. “It seemed logical that he couldn’t eat while he was struggling to breathe.”
Later, while recovering at home, Nicholas began crying so loudly and consistently that he developed an umbilical hernia. He was diagnosed with gastroesophageal reflux disease (GERD) and put on medication. When he was 6 months old, he was referred to a pediatric gastroenterologist.
“Finally, when Nicholas was 8 months old, our gastroenterologist had a combination of medications that was working,” Melody said. “Nicholas did well for about a week, then developed a gastrointestinal infection and was hospitalized for seven days. He was discharged with a nasogastric tube and no concrete diagnosis.”
After a week of feeding through the NG tube that passed through his nose and esophagus into his stomach, Nicholas started vomiting. “We didn’t know whether it was a relapse, or something new. But we did know that his gut was in bad shape. His gastric emptying was four times slower than it should have been,” Melody said.
By the time Nicholas was 11 months old, he’d undergone two major surgeries: a pyloroplasty in which the valve regulating the movement of food to the intestines was repaired, allowing his stomach to relax and empty its contents, and a fundoplication for GERD, to strengthen the valve between the esophagus and stomach, preventing stomach acid from backing up into the esophagus.
Things began to improve for Nicholas, but when he was close to 15 months old, he was hospitalized with blood sugar swings. Later, he had other symptoms associated with mitochondrial dysfunction, including mild to moderate hypotonia, or low muscle tone.
“We still weren’t thinking of mito at this point,” Melody said. “Our gastroenterologist had mentioned it as a possibility but there really wasn’t enough evidence to take mito seriously. Nicholas is developmentally delayed in terms of his motor skills but he’s cognitively bright. Many doctors feel you have to have a cognitive disorder for a mito diagnosis.”
It took the diagnosis of a mitochondrial disorder in their second child for the couple to recognize that Nicholas was affected as well.
Nathan
Nicholas was 28 months old the day Nathan was born. Like his older brother, he came into the world with little interest in eating, and no one could figure out why. But his parents were thrilled that he was healthy and didn’t require a stay in the NICU immediately after birth like his brother had.
After his circumcision 23 hours later, Nathan had a dusky spell and difficulty breathing. He was moved to the NICU for observation.
“Eventually, his breathing returned to normal,” Melody added. “He spent four days in the NICU, where he was treated for a possible infection, but they could never grow anything on culture. Then came the jaundice, which lasted for about three months. Later, when we trialed him off breast milk, he lost the jaundice so we knew it was from breastfeeding.”
About that time, they began to notice that Nathan had problems with his neck. By then, 2-year-old Nicholas was receiving regular occupational and developmental therapy at home.
“Nicholas’ therapists told us that Nathan should have been holding up his head earlier,” Melody said. “So at just 4 months, he started therapy and saw his first neurologist.” For Nathan, the long cycle of unexplained health problems and visits to specialists had begun.
As he grew older, his developmental delay grew more marked. Nathan couldn’t hold up his head until the age of 7 months; he didn’t sit until he’d reached 9 months; and he began crawling at 13 months. His legs were weaker than his arms, and he had difficulty coordinating them.
Like Nicholas, he’d been diagnosed with GERD. Because his parents recognized the symptoms of GERD early on, Nathan’s disorder has remained well controlled. He’d also had ear tubes implanted following repeated ear infections.
“We thought the ear infections might have been affecting his balance," Melody said. “It was one thing after another, and always something that could be explained away. We were seeing a lot of specialists and they were treating each diagnosis separately without seeing the big picture.”
Mito was first mentioned as a possible diagnosis when Nathan was about a year old, but his basic chromosomal testing came back normal. At the age of 16 months, he had a muscle biopsy done to test for the presence of a mitochondrial disease.
“It took us nearly three months to get the results, and they were suggestive of mito,” Melody said. “Our neurologist recognized that mito was beyond her scope of knowledge and referred us to another neurologist.
“At this point everyone was baffled because Nathan started walking. He was just shy of 19 months and had been making enormous progress in therapy. We were thinking he might walk by the time he was two, but he had a sudden and remarkable improvement in his motor skills.”
Nathan’s new pediatric neurologist ordered basic blood work and a urinalysis, which came back normal, further confusing the issue. The neurologist ordered a spinal tap and an MRI with spectroscopy to examine the chemical makeup of Nathan’s brain. The MRI scan appeared normal, but the spinal tap came back with mixed results.
“So the neurologist sent us to genetics. We were told that Nathan and Nicholas looked too good to have mito. They can walk and talk, and they’re bright.”
In the meantime, Melody had joined an online mito discussion group. “Someone from the online community mentioned Dr. Koenig and raved about her. She said, ‘You really need to see her. She’s wonderful and she’s right there in your neighborhood.’”
Mary Kay Koenig, M.D., is a child and adolescent neurologist affiliated with Children’s Memorial Hermann Hospital and an assistant professor of pediatrics at The University of Texas Medical School at Houston. An expert in mitochondrial diseases, she is director of UT’s Neuro-Metabolic and Mitochondrial Clinic.
Four weeks later, they arrived in Koenig’s office armed with more than 700 pages of medical records for their two sons.
“She did a thorough evaluation of both of them,” Melody said. “She was wonderful with the boys. After all they’ve been through with the medical community, they’re not very trusting of doctors. When we left, Nicholas asked when they’d get to see her again.”
Dr. Koenig said: “When they came to me, Nicholas and Nathan didn’t have an official diagnosis. Since that time we’ve been able to confirm the diagnosis with blood work.”
Based on the results, Koenig started Nicholas and Nathan on supplements, including CoQ10, carnitine, folate and riboflavin, among others.
“Every mito doctor in the country has his or her own set of preferred supplements,” Dr. Koenig said. “Every patient gets CoQ10 and carnitine but other supplements are given in different combination, depending on the physician.
“The one commonality we do see in patients is that those followed by doctors who are not specialists in mito get doses that are not high enough. Usually, the first thing I do with patients is triple or even quadruple the supplements they’re receiving.”
Under treatment with Dr. Koenig, Nicholas has gone from doing two sit- ups a day to 20. “The boys’ therapists have raved about their remarkable change in stamina and strength,” Melody said. “They aren’t exhausted all the time. They’re slowly improving."