Mitochondrial Disease: the damaging rhetoric of Hollywood

admin  ∼  February 5, 2016  ∼  Patient Consultations Patient Advocacy Mitochondrial disease Next gen sequencing Exome Muscle biopsy Gene testing Symptom Diagnose Nuclear DNA Re-diagnosed Metabolic Whole Exome Sequencing (WES) Test Evaluation Medical Abuse Somatoform Treatment chronic disease Living with

VMP's Dr Fran Kendall Factoid Friday Blog on Rare Diseases


This week, the mitochondrial and rare disease community suffered a significant blow with the airing of the much anticipated Chicago Med episode highlighting a young girl with presumed mitochondrial disease, discounted on air as a waste basket diagnosis, with no acknowledgement that mitochondrial disease is a devastating scientifically recognized group of disorders affecting 1 in 5,000 people.

Evaluating emergency room physicians determined that this child could not possibly have mitochondrial disease because she had not undergone a muscle biopsy and that her father falsely diagnosed her by utilizing searches on the Internet. However, they failed to address the fact that this girl did have both a G-tube and a central line implanted by other physicians who had evaluated this child and come to some determination that these interventions were medically necessary.

Nonetheless, as the show progressed, there appeared to be psychological factors impacting this child and her medical presentation. Certain symptoms resolved spontaneously and conversations with Chicago Med medical providers indicated that there were some psychological overlay to her symptomatology. However, despite what would appear to be legitimate concerns based on the presented case, at no time did they even seek information from her treating physicians before coming to their damning conclusion. 

In this specific case perhaps there were indeed factors at play other than true system pathology. Given that possibility then why are we so angry by this storyline?  Because the writers and producers carelessly lumped mitochondrial disease under the broad heading of the child medical abuse umbrella. Their implications were clear – mitochondrial disease is a non-disorder and people presenting with that diagnosis are likely to have a conversion disorder or fictitious parental reporting and exaggeration of minimal or nonexistent symptoms. As such, one would extrapolate that those affected do not have real disease and those who diagnose and treat these patients are dabbling in the fringes of medical science placing people in this wastebasket category for a number of poorly defined reasons.

Since the premise upon which they built their case is grossly inadequate I'm going to use this opportunity to educate the naysayers and misinformed. First and foremost is to state emphatically that mitochondrial disease is NOT a wastebasket diagnosis but rather a group of disorders causing a multitude of typically progressive problems leading to considerable morbidity and mortality for affected individuals. First described in the 1930’s in patients with a neurodegenerative course, mitochondrial disease now encompasses multiple subtypes with an incidence of 1 in 5000.   Since the 1980's, we have gone from describing the disorders to undertaking FDA regulated clinical treatment trials in an attempt to cure these disorders or, at the very least, improve the quality of life for affected individuals.

For those that insist that these diseases are not real, I have seen my patients' bodies deteriorate, their brains disintegrate, and have watched them transform into a shell of their former selves. Over the course of my 25 year career I have borne witness to dozens of children and adults die from these diseases, I have attended their funerals, cried with their families and held the hands of their grieving loved ones as they walked the hardest journey of all. To deny the existence of these disorders is a travesty and disrespectful to those who have lost their battle after mounting a brave and courageous fight.

The second important piece of information to disseminate is that mitochondrial disease is not fringe medicine. I am a hard-core science-based physician trained at Harvard, the former chairman of my department of genetics and previous owner of a biotech company. Using rapidly evolving technology we are instead on the cutting edge of science advancing medicine with our groundbreaking research and clinical work.  

While complicated and sometimes not straightforward, the diagnosis of a patient with mitochondrial disease is based on the identification of a constellation of biochemical, enzymatic, and molecular abnormalities since there is no single test that will definitively diagnosis a mitochondrial disorder in ALL cases. Utilizing a tiered system of investigation, we carefully gather data to determine at the end of the road whether or not our patient meets adequate criteria to be classified as a mitochondrial disease patient. Do they have elevated lactate or CPK levels, did we identify a common or other mutation, is enzymology indicated and, if so, was it abnormal? In addition, there are published guidelines including the Bernier and Morava criteria that assist with the diagnostic process. When all is said and done, we make a decision based on as much scientific data as possible.

However, some patients defy testing and, despite our best efforts, fail to be clearly classified and placed into a clean diagnostic category. I follow patients with a neurogenerative course due to Leigh disease who have not been identified to carry a gene mutation despite utilizing advanced genomics.  Does that mean that they are healthy and have no underlying disorder? Of course not.

In some cases, the diagnosis of mitochondrial disease is considered a strong possibility based on clinical symptomatology without an abundance of testing support simply because we recognize that there are limitations in current medical science OR because insurance, particularly state Medicaid and Medicare, won't cover the needed diagnostic testing. But because ambiguity breeds suspect, I will be clear with patients and families and referring physicians that I have exhausted the limits of currently available diagnostic tools and why I still feel it may be beneficial to consider this diagnosis in a given patient. However, I do strive to document as many of the clinical symptoms as possible despite the negative or non-diagnostic workup (or limited workup) to date.  For example, if someone has significant constipation or abdominal bloating after eating, I will recommend gastric emptying studies and dysmotility testing to confirm pathophysiology. In one case, approximately six or seven years ago, I did just that in a young woman who was being labeled as possible conversion disorder. When I documented her dysmotility, her other physicians suddenly approached her differently enabling her to get the care she so desperately needed. Sadly, this young woman passed away a few years ago but her parents no longer had to struggle to justify her needs during her battle. Nonetheless, the lack of a clear diagnosis in a subset of the population does not automatically translate into child medical abuse or conversion disorder for the community at large.

So, why is this happening to a population that is suffering and loses members every day to the devastation of this all too real disease process? The answer is as complicated as the disease itself and includes poor awareness by the public at large, lack of understanding by the medical profession who either dismisses the diagnosis outright or attempts to make the diagnosis without proper education and training leading to misdiagnosis, and the overzealous use and misinterpretation of some diagnostic tools.

To emphasize my point regarding public awareness, the reason so many people are devastated by the recent Chicago Med episode is because we recognize in today's world that, sadly, many people utilize social media and the entertainment industry as a source of all truth and information.  As such, the propagation of mistruths and falsehoods through those mediums can be rapid and widespread leading to dilution of the truth and acceptance of misperceptions as hardened facts. 

Another problem we face is that most physicians and other healthcare providers know little to nothing about mitochondrial disease. Although I personally now educate both nursing and med students about these diseases, during my own training, to include both medical school and residency, I learned absolutely nothing at all about mito. It was not until I began fellowship at Boston Children's and Harvard Medical School that I began my mitochondrial disease education. This lack of knowledge in the general clinical environment typically leads to ignorance and dismissal.  So while education is key, it is unrealistic to think that a handful of mitochondrial experts can educate an entire physician population using standard educational techniques such as symposiums and Grand Rounds.  I myself, as well as many colleagues, have flown halfway across the country to present at various hospital settings only to face an audience of merely 10 to 20 individuals. While the education of even one person is important, it is not a good utilization of limited resources. As such, we must seek out and explore alternative educational mechanisms.  It is for this reason that we strive to secure funding from Foundations and Corporations for our educational blogs.  This venue allows us to reach thousands of individuals for the cost of my time only. Without leaving the comfort of my home or office, I can provide 25 years of knowledge regarding a variety of subjects to a widespread and broad audience with the click of a button.

While complete ignorance regarding these diseases can be devastating to patients and families seeking help, well-meaning physicians with a limited knowledge base who nonetheless deem themselves to be expert enough can be almost as damaging. For example, I have seen multiple patients who, as part of an evaluation for presumed mitochondrial or other muscle disease, have undergone muscle biopsies only to have their work up limited to muscle histology. While histology can be extremely helpful if it identifies some of the pathognomonic changes seen with mitochondrial disease, the absence of ragged red fibers, present in only 2.5% of cases, does not eliminate this diagnostic possibility. Alternatively, a number of patients over 50 who are found to have ragged red fibers on muscle biopsy have been diagnosed with mitochondrial disease only to discover upon consultation with a mitochondrial expert that the presence of this histological change in that age group is commonplace and not reflective of a disease process. I have also seen multiple patients given the diagnosis based on isolated elevations of lactate, not confirmed by repeated levels or correlated with elevated alanine to lysine ratios required to eliminate processing or exercise/eating artifacts.

Unfortunately, the overzealous use of some diagnostic tools, specifically muscle biopsies, by some providers (often obtained prior to completing a more exhaustive investigation to include but not limited to chromosome studies or other gene testing) led to mislabeling of many patients who were ultimately diagnosed with other disorders causing doubt among the extended physician community about the validity of a mito diagnosis. Personally, I have re-diagnosed dozens and dozens of presumed mitochondrial patients with seizure disorder mutations, neurodevelopmental syndromes, myasthenia gravis, movement disorders and even rickets. Fortunately, with the advent of advanced genomics, fewer muscle biopsies are being obtained as a first line of investigation leading to a more accurate classification of patients into their appropriate diagnostic basket. And although advanced genomics is a remarkable advancement in medical science many individuals who order and interpret the studies are not qualified to do so leading to additional confusion about the implications of the information.

While the patient population undergoing evaluation for mitochondrial disease may not have direct access to mitochondrial experts during their initial evaluation or are unaware that their evaluating physician has a limited knowledge base, they should strive to seek a second opinion consultation by a true mitochondrial disease expert to avoid misinterpretation of their testing results or misdiagnosis.

In summary, mitochondrial disease is a scientifically recognized diagnosis effecting thousands of individuals leading to severe morbidity and mortality for affected patients. While wedded in hard-core science, the diagnosis is complex requiring a complicated algorithm of testing which sometimes fall short in classifying all patients evaluated leaving some in a diagnostic quandary and vulnerable to a poorly informed populace. Ongoing educational endeavors utilizing nontraditional mechanisms such as this blog, improvement in testing modalities and screening studies to reduce ambiguity of diagnosis, and ongoing advocacy by experts and the patient population will ultimately prevail rewriting the inaccurate script currently being disseminated.

All truths are easy to understand once they are discovered; the point is to discover them. Galileo Galilei

Sincerely,

Fran Kendall, MD

Founder, Managing Director of VMP Genetics, Clinical Biochemical Geneticist

The above blog was funded in part by a generous donation from the Foot Foundation. More can be learned at www.footfoundation.org

This post is not meant to be a recommendation or a substitute for professional advice and services rendered by qualified doctors, allied medical personnel, and other professional services. The responsibility for any use of this information, or for proper medical treatment, rests with you.