Rare Disease Awareness
Written by Wayne Rosenfield, PhD
She was a beautiful child. She was so good-looking that her cuteness was almost a caricature. Her blonde hair fell straight onto her shoulders, with bangs that were cut to reveal her forehead, accentuating her big blue eyes. Her nose was small and turned up ever so slightly. She was petite, even for a seven-year-old. She looked me straight in the eye nearly continuously and was almost always smiling. Her mood was one of happiness and she was a joy to be around. If a cartoonist had set out to convey his conception of a living doll, this might have been the result. There were a lot of toys available in the room, but her attention was exclusively directed toward me. She seemed to be oblivious to the presence of her mother or the female doctoral student also in the room with us.
The child’s mother reported that her daughter loved music. With very little instruction the girl seemed to just intuitively know how to play the piano, her mother noted with some pride. The child had been a colicky infant, but she developed language remarkably and she was now quite verbal. Despite some fine motor problems, the child was quite social in school, although mostly oriented toward the adults.
She continued to ignore the room full of toys and started climbing onto my lap. I have performed a great number of psychological assessments, but this is the only time that this happened. I must have looked startled.
“This is what happens,” her mother said. “She is overly friendly with strangers. She took a strange man’s hand in the mall and asked if she could go with him. Fortunately, I was right there.”
My student and I asked a few diagnostically important questions to evaluate some important hypotheses. There did not appear to be a history of abuse or exploitation, although the child was clearly at great risk. We could identify no other relevant psychological factors to explain the child’s profound impairment of social boundaries. We had no solution to this puzzle.
The mother revealed that she has been distressed by the child’s behavior for several years. The pediatrician thought that the child was mildly uncoordinated, but otherwise physically healthy. This family’s experience in the ambiguous world of rare disease had begun.
I had been involved in the broader issue of rare disease for many years through my association with the communities affected by Gaucher Disease and other lysosomal disorders. However, those experiences did not help me to understand this child. My rare disease experiences did tell me, though, that well-defined, enduring observations that appear to have little relationship with each other, may have a common cause.
Science, I learned many years ago, attempts to describe, explain, predict, modify, and control observed phenomena. And a good theory will explain the observations in the simplest manner. “A good theory is parsimonious,” I can still hear my professor saying. The answers are here, if we can only ask the right questions. And then we must separate the signal from the noise.
The Gaucher Disease experience, to use the example of the most common lysosomal disorder, required scientists to explain how a large spleen may be related to a painful leg, or how a nosebleed may be related to a flask-shaped long bone. All of those observations are united by a single, parsimonious, explanatory theory: A diagnosis of Gaucher Disease. And in retrospect, when a diagnosis is confirmed, it is easy to wonder how it had ever been missed.
But the reality is that rare disorders are, well, really rare. The constellation of indicators is present, and evident to multiple observers. But the explanation is not handed to us. In a movie, the sets, costumes, props, dialogue, effects, and even the music are integrated to tell us a story. A scientist has a collection of observations, but no narrator to tell him where to look.
My young patient did not come to the clinic with a book about her life. Could there be a single theory to describe and explain my observations? I could not flip ahead to see how it all turns out. I would be helping to write her life’s story, and I am not ashamed to say that I too was distressed by the ambiguity. Families affected by rare disorders commonly wait almost five years until someone puts the pieces together. And a delay of decades is not uncommon.
Psychologists have some very good science-based methods of assessment, at least with regard to the most common issues affecting children and adolescents. Yet there was no single test or algorithm to put the observations together for us with this child. We still had observations that represented ill-fitted puzzle pieces. What does it mean for a good looking and happy child with a history of colic to have a friendly personality, exceptional musical ability, some impaired coordination, and an extraordinary absence of apprehension around strangers?
I derive a very special type of joy from seeing a student do our work better than me. And my almost-a-psychologist student developed the parsimonious explanation that we call a theory or, as in this case, a diagnosis. As my student discovered, hidden within the pages of references on behavioral genetics, fewer than 1 in 10,000 people will have a certain deletion on chromosome 7. And such people are sometimes described as elfin, musical, and socially uninhibited.
There is a certain satisfaction, but also some distress in learning that the symptoms fit a known pattern. At a follow-up meeting, the mother cried when we told her that the constellation of her daughter’s characteristics matched Williams Syndrome, one of the rare genetic disorders.
According to the National Organization for Rare Disorders,
People with rare diseases have tremendous unmet needs, including misdiagnosis, a long time to finally receive a correct diagnosis, and when they do, 95% have no treatment with ZERO CURES (http://rarediseaseday.us/).
Research will help us to find the answers. And we have a lot of work yet to do.
Read more about Wayne’s journey with Gaucher in his memoir, Great Necessities.