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2 THE ROAD TO A DIAGNOSIS
Corey Haas was born on September 22, 2000. After an uneventful pregnancy, Nancy
gave birth to the blond, blue-eyed baby, who weighed in at a respectable nine
pounds.
For the first few months, all was perfect and he hit his developmental milestones
ahead of schedule. “Corey was a happy baby. But the babysitter noticed that he
wasn’t reaching for things right in front of him, like other babies do,” recalled Nancy.
She worked in an office nearby, while Ethan commuted more than an hour each way
to and from his job at International Paper, so they often weren’t with their son during
the day. Corey’s parents and the babysitter wondered about Corey’s peculiar habit
of staring, enthralled, at lit bulbs, for far longer than anyone else would or could. When
the babysitter commented that Corey never made eye contact with her when
drinking his bottle, Nancy realized that she’d been aware of this too, but thought he
was just too young to focus.
As the weeks went on, the new mother felt an ember of fear whenever she’d call her
son’s name and he’d turn, but just stare in her general direction; she didn’t feel as if he
was seeing her. Then Nancy noticed that he played only with toys that were lit up or
that were lying in a patch of sunlight on the carpet. Something was wrong with Corey.
By six months of age, the problem became more pronounced. Not only couldn’t
Corey focus, but now his eyes wandered, flicking back and forth, his left eye worse
than his right. This painless but unsettling condition, which the Haas family later learned
is called nystagmus, is common in people who have albinism. Perhaps because
Corey’s hair and skin had color, the local pediatrician reassured the concerned
parents that albinism didn’t seem likely, and that the boy would probably outgrow the
troubling symptoms.
Corey’s local pediatrician apparently made no notes that indicated he suspected a
genetic disease, and this is understandable; such conditions usually bring a swath of
signs and symptoms, such as developmental delay, unusual facial features, defects in
major organs, or constant colds from a suppressed immune system. Corey was a
chubby, vibrant picture of health, adorable and active. But the pediatrician, noting at
the six-month exam Corey’s occasionally crossed eyes, was sufficiently concerned to
refer him to the ophthalmologist Gregory Pinto in nearby Saratoga Springs, the first in a
series of eye specialists who would gradually zero in on the diagnosis. Nancy and
Ethan were concerned, but not alarmed. Perhaps his visual system was just developing
a little slowly— not all babies focus on their parent’s faces in the first weeks of life.
Corey’s wandering eyes seemed like something that would be simple to fix, if the
condition didn’t clear up on its own.
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Dr. Gregory Pinto
Corey’s eyes had all the right parts, but the doctor noted that the back of his eyes had
unusually pale areas, “blond fundi” in the medical lingo. The most telling of the
doctor’s observations was Corey’s fascination with lights. Dr. Pinto had seen that
before, in people of limited sight trying to “self-stimulate,” he told Nancy.
Except for his eyesight, Corey seemed fine, eager to go from immobile infant to active
toddler. He loved to explore. At eight months, no longer content to sit and crawl,
Corey was already hauling himself upright, but he was clumsy. He’d bump into things,
especially when the room was dimly lit. And Corey continued to stare at lights,
mesmerized.
Like a seedling seeking the sun, Corey continued to pull himself up and grab toward
the lamps in the small living room. Soon he was cruising and then walking. Once he
could no longer feel the surface of the shaggy carpet beneath him with his hands and
lower legs, his internal feedback system was gone, and the bumping into things
worsened. Yet in other ways he was right on track. He could utter a few words and
even draw simple shapes. He was learning to compensate with his better-functioning
senses.
At the next eye exam, Dr. Pinto picked up on a change for the worse. “Corey had
started to show signs of visual difficulty. Sometimes he would crawl right into a table
leg. He didn’t follow objects as well as he previously had. His eyes now crossed slightly
and, most significantly, he was quite nearsighted,” recalls the ophthalmologist. The
doctor was concerned at the rapid deterioration of Corey’s vision and sent him to a
pediatric ophthalmology subspecialist, Dr. John Simon, an Albany physician who had
a satellite office near the Haases’ home. He confirmed Dr. Pinto’s findings, and
prescribed Corey’s first glasses when the boy was ten months old. At a follow-up visit
near the end of 2001, Dr. Simon discovered some new signs: Corey’s left eye turned
inward, and his irises let light through in spots, as if pierced with tiny holes. But Corey
was still too young for anyone to really tell what was happening, other than extreme
nearsightedness. Many kids simply outgrew early visual problems. It was too early for a
definitive diagnosis, but in the meantime, the glasses would help.
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Dr. John Simon
Corey continued to develop at a normal pace, but his vision worsened, despite
doubling the correction in his glasses. At his last visit with Dr. Pinto, Corey was in the
throes of the “terrible twos.” He wouldn’t keep still long enough for a complete retinal
exam, but the doctor saw enough to realize that Corey was trying to look at objects
and identify them, but he couldn’t really see them. And he still stared, captivated, at
the lights.
In early 2003 came the first critical connection that would catapult Corey toward
gene therapy. Although he did not yet have a diagnosis, Corey saw so poorly that he
was eligible for the New York State Early Intervention program, which assists young
children who have disabilities or developmental delay. One day, the early-intervention
provider, visiting the Haas home, mentioned in passing that she had been talking to
another parent whose child had a similar visual problem. “Where did the parent take
her child?” Nancy asked.
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Boston Children’s Hospital is about a five-hour drive from the southern tier of the
Adirondacks, counting bathroom stops and the inevitable traffic on the Mass Pike. In
January, an ice storm or blizzard can derail travel plans, as can the squalls that
materialize out of nowhere along the barren stretch of interstate in the Berkshires,
whipping up ephemeral mini-tornadoes of blinding snow. But luck was with the Haas
family on a January day in 2003. The air was clear and crisp, and they made it to
Corey’s first appointment at Boston Children’s Hospital in record time.
They instantly liked Anne Fulton, an ophthalmologist specializing in diseases of the
retina in young children. Her shock of thick white-gray hair looked a little like Corey’s
blond mop. Dr. Fulton listened intently to Nancy and Ethan and wrote in the medical
chart, “Corey’s visual behaviors are described as seeing well in good light. In low light,
he crashes into the furniture, and they have wondered if this might be because he is
looking at the lamp instead of where he is going. He watches the TV at an angle.”
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Dr. Anne Fulton
The next day, Corey was anesthetized to keep him still and given eyedrops to dilate his
pupils, to do an electroretinogram, or ERG. This test shows the retinas’ responses to
flashes of light, and is normally a curve that dips and then sharply rises.
Corey’s ERG was as flat as an Iowa cornfield.
Ophthalmologists knew that a flat ERG is a definitive sign of a certain class of retinal
diseases, but since Dr. Fulton rarely had seen such a profound lack of a response, she
double-checked her equipment. It was fine. The problem was with Corey’s eyes. Light
energy wasn’t getting to his brain.
Once Corey awakened from the anesthetic, Dr. Fulton donned a device resembling a
miner’s helmet and gently peered at each of the boy’s retinas, under light so intense it
often made children (and some adults) scream. Not Corey. If he hadn’t been so
fascinated with all the paraphernalia, and so oblivious to the penetrating light that
was much brighter than he was used to, it might have been harder to keep him still.
But Dr. Fulton got a good look. In each eye, she saw that the macula, the pale area
near the point that provides the sharpest vision, was too pale. It was an ominous sign.
Dr. Fulton’s tentative diagnosis: albinism. Corey’s stumbling in dim light suggested night
blindness, but the family’s pale coloring and the observation that both Nancy’s and
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Corey’s irises let in light through tiny holes suggested albinism. Perhaps Nancy actually
had a very mild case of albinism, and Ethan was a carrier of the same type, and their
individual mutations combined in a way that more severely affected their son’s eyes.
The various types of albinism are recessive, passed from unaffected carrier parents, so
the fact that neither Ethan nor Nancy knew of any affected relatives didn’t matter.
Albinism could be passed, silently, for generations. Corey had already tested negative
for the most common type of albinism, but maybe the Haas family had a rare or even
unique form of the condition that affected mostly the eyes.
Eight months later, in the fall of 2003, Corey turned three and started preschool. His
world now consisted of shadows even when he was in a normally lit room, and in a
brightly lit room he had extreme tunnel vision. Today he acts out this early memory,
tilting his head to show what he once had to do to position an object in the center of
his shrinking visual field.
That October, Corey returned to Boston Children’s Hospital for a more complete
workup. Wen-Hann Tan, a pediatrician and geneticist, examined the squirming
toddler, checking for hints of “dysmorphology”— known informally in some genetics
circles as an exam for an FLK, or funny-looking kid. People with genetic syndromes
often have unusual facial features that alone might simply seem quirky, but taken
together may point a perceptive clinician to check particular genes and
chromosomes. Corey sat still while Dr. Tan meticulously measured the dimensions of his
ears, nose, and jaw; opened his mouth wide to scrutinize his palate; noted the spacing
and slant of his eyes; and measured the space between his upper lip and nose.
Corey’s face was cherubic, bearing not a hint of anything awry.
Dr. Tan
Still not ready to abandon the possibility of albinism, Dr. Fulton asked the attending
physician in genetics and metabolism at the hospital, David Harris, to test Corey,
Nancy, and Ethan for two rare types of the disorder. In albinism, an enzyme deficiency
blocks production of melanin pigment. Without the pigment, the eyes can’t form
good images, and the optic nerve pathways to the brain don’t develop normally. The
visual field shrinks, and the eyes jiggle back and forth. Again, Corey’s results were
normal. His eyes weren’t normal, but it wasn’t because of albinism. What was wrong?
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With the more common explanation, albinism, now ruled out, retinal degeneration was
rising to the top of the list of possible diagnoses. Corey’s peripheral light-sensing cells,
his rods, and possibly his central color-vision cones, were either wasting away or
ignoring incoming signals. This was more dire than albinism.
Corey, Ethan, and Nancy returned to Boston Children’s Hospital in May 2004. Dr.
Fulton’s notes from that visit chronicle a growing boy, interspersing technical terms
such as diopter and esotropia (turning in of the eye) with wiggly. “Corey is active. He
is an explorer.” Her analysis of the specific visual deficits over time now led her to
suggest a condition called Leber congenital amaurosis (LCA). Back in 1998, she’d
been part of the team that identified the gene that would turn out to be behind
Corey’s condition. Now she wrote in his chart, “Corey’s visual acuities are too good, or
much better than in many children with LCA, for us to think of LCA in a conventional
way.”
It was the first mention of what would ultimately be the correct answer.