 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."
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