An Okapi in a Field of Zebras: On Rare Manifestations of Rare Diseases

by Kara Ayik
RARE Parent & Caregiver

An okapi has stripes like a zebra, and looks quite a lot like one, but it isn’t a zebra. Although once classified as a rainforest zebra, in fact it’s actually more closely related to a giraffe. My adult son, diagnosed at age three with a rare lysosomal storage disease called Acid Sphingomyelinase Deficiency, (ASMD) grew up like the rare and puzzling okapi. Unlike most individuals diagnosed with ASMD, his presentation, or phenotype, more closely resembled that of one of the mucopolysaccharidosis (MPS) diseases. He had symptoms he shouldn’t have, according to what I first read about the disease, including the description on our
family support organization’s website. I was left worried and confused because the internet descriptions led me to anticipate only the most commonly
shared features of ASMD, such as an enlarged spleen and liver and problems with lung infiltrates. His presentation of ASMD was, as one noted authority on the
disease observed, “a puzzle.”

But in fact, my son is not the only okapi in the rare disease world. Other individuals with rare diseases or their caregivers have similarly expressed confusion and concern about unexpected manifestations of their respective rare diseases. Essentially, the medical community’s reluctance to incorporate these symptoms into the disease descriptions– or even to acknowledge them—is a serious problem because such an incomplete picture of a rare disease creates consequences.

One evening, after my son, then 17, had just spoken at a fundraising gala, another of the world’s leading authorities on ASMD informed me that I was definitely mistaken about my son’s diagnosis. The authority stated, without hesitation, that my son had one of the MPS diseases, not ASMD. For just a split second, I paused in a moment of shock. Could it be? Then the emotion quickly passed. My son’s documented genetic mutations for ASMD had been identified over a decade earlier, and a geneticist had already tested him for the MPS diseases and had even ordered a microarray. Right in that moment, the knowledge of my son’s specific genetic mutations and labs tests verifying his ASMD diagnosis brought me some peace. Numbers don’t lie. (The expert, once he looked at the mutations, realized he was mistaken. In a trust re-building move, he later apologized kindly.)

But it wasn’t the first time I heard, ASMD? I don’t think so. Years after the diagnosis, I began turning to professionals outside of the ASMD community for answers. One genetic counselor asked me for permission to share some pictures and a list of symptoms I had noted as unusual. She showed them to two different geneticists, and the verdict was unanimous—my son most likely had one of the MPS diseases.  And just last year, while viewing a physician expert discussing ASMD for an audience of his peers, I had a forehead-slapping moment as the physician adamantly instructed his peers that distinctive facial features are “definitely” not part of the ASMD profile.

The problem is worthy of exploring given the potential consequences, all of which my son and I have experienced, which include:

1. Denial of insurance coverage when the manifestations or symptoms do not match the published literature, popular and scholarly, such as physical therapy services for joint contractures and stiff joints. The physician reviewer in our case quoted descriptions of ASMD from the internet, which did not include joint stiffness and contractures, as validation for denial of coverage.
2. Second diagnostic odysseys are initiated when individuals with the rare manifestations or their caregivers seek answers when their providers don’t have them. The basic human need for explanations and closure may lead to testing which may be painful, scary, or costly, and all of which may be unnecessary.
3. Failure to consider screening, evaluation, or treatment for manifestations that don’t align with the scholarly or popular literature written to inform stakeholders.
4. Exacerbation of the loneliness individuals and their family members may feel when the individuals don’t seem to fit in a patient group because of rare manifestations that aren’t acknowledged by the medical community as characteristic of the disease.
5. Reluctance and refusal of family support organizations to list these rarer symptoms in their patient and physician education materials, even when asked, because the popular and medical literature does not document them, and thus the physician reviewing the proposed list does not support their inclusion. This reluctance and refusal may contribute to a lack of confidence in the organization and a sense of exclusion and dismissal for the diagnosed individual and their family.

My belief is that one of the root causes of the dubious response to someone presenting with uncommon manifestations of a rare disease is the way Westerners have been taught to think. As a lecturer, I like to incorporate the work of David A. Livermore, author of CQ: Improving Your CQ to Engage Our Multicultural World, ¹ as we study Native American worldview. In his book, Livermore explains Westerners’ bounded set logic and narrow category width in making sense of the world. In brief, Westerners define objects by determining whether or not they meet a specific set of criteria. Fitting in is a yes or no proposition, and the criteria we establish are generally quite strict, forming a narrow category width. These distinctions create a rigid boundary between what is and what is not. Livermore provides an example of this logic holding up an apple as an example. For a Western thinker, an apple is an edible fruit– red, green, yellow, perhaps pink– of a certain size and maturity. An apple bud or blossom cannot be considered an apple. But for a Native American who sees the world through “centered sets”¹, an apple bud and an apple blossom are also considered apples. My son’s constellation of symptoms means that for Western bounded-set thinkers using narrow category width, his presentation falls outside of the classification of what defines ASMD.

The second explanation for this pattern of skeptical resistance? Pressure. On one hand, it’s no secret that we live in a litigious society formed in part by grieving, sometimes angry or hurt parents, and healthcare professionals are afraid of making mistakes, not solely for their own liability, but also for the protection of their own egos. No one wants to feel foolish or incompetent, and most certainly no one wants face any threat of malpractice.  It is less risky to stick with the status quo on what the readily accessible North American or European academic literature states as fitting the description of a disease like ASMD. (It’s worth noting that older papers and those published in less affluent countries are not always accessed in a deep dive even when they provide insights and valid explanations for less common manifestations.) On the other hand, there is the commodity of time. Given the corporate expectations for physicians to aggressively limit the amount of time spent on each patient, the pressure to speed through the visits leaves little time for listening and focused research. This time constraint is particularly exacerbated in underserved, suburban areas with a high population of patients with low-reimbursement insurance coverage like my own in the Central Valley of California.

Those healthcare professionals whom I approached for validation, explanation, or documentation of my son’s rarer manifestations typically offered the same response. They would shift their eyes to the side, tilt their head, and mumble some variation of, “Uh, well, yes… it’s certainly a spectrum disease, and not all individuals are affected the same way.” In the end, I found enough scholarly research about lysosomal storage disease overlap and ASMD case studies to satisfy my need for answers.  Occasionally, I made a fruitless pitch for a more comprehensive disease description to different entities.  But I want better experiences for the people who will travel this same path, perhaps for those with less formal education than I have been privileged to have, for those who are more passive and reticent in the face of cultural and hierarchical norms, or for those who are under-resourced and less able to press for the answers and needed care.

My expectations are not unrealistic. I do not expect physicians and genetic counselors to memorize an exhaustive list of the possible symptoms of the approximately 10,000 rare diseases that exist. What needs to be examined is the tendency to operate from a worldview that resists acknowledging the rarer symptoms and recognizing the more unusual presentations as actually normal for that rare disease.

Positive change begins with a willingness to begin to build new paradigms around defining and characterizing rare diseases, particularly in medical literature, and also to address the pressures which drive fears and egos in influencing the healthcare provider’s words and conclusions.

As a postscript, I recently received a group photo when e-mailing the Niemann Pick (ASMD) Family Support Association in China regarding our children’s book, Extraordinary! In the foreground, I spotted a handsome little boy in a light blue coat whose joint contractures at the elbow and facial features made me instantly think of my son. Another little okapi. I made a special request that little boy receive his own copy of our book. Human beings want to belong, and they deserve to live their best lives, which is often made possible through the gift of medicine as practiced by ethical and enlightened providers.

Livermore, D. CQ: Improving Your CQ to Engage Our Multicultural. World Baker Academic; 2009.