Readers Respond to Our Call for Help With a Diagnosis

I’ve read Angel’s medical records, but it’s unclear whether she has taken or does take any other medications. Has she ever been diagnosed/treated for ADHD (or otherwise taken medications RXed for it)? RX amphetamines now come w warnings for Rhabdo. It would be worth clarifying whether she’s taking any such drugs to help with school, whether prescribed or not, or recreationally. I see she denies any recreational drug use, but lots of students take adderall during crunch time (and share with friends) and she may not have wanted, or even thought it relevant to mention that during her hospital admissions. [As an aside, some years ago I was prescribed Ritalin (methylphenidate) for ADHD. Several times a month, I would become debilitated by excruciating idiopathic body pain that traveled from my metatarsal bones all the way up to my neck & skull over the course of a a few hours. Over the course of a year or two I wasted away, losing muscle mass, becoming too thin, and the incidents of body pain increased as well. Rhabdo was never explored as my blood work was normal except for anemia. Eventually I was diagnosed with fibromyalgia, which went into remission after I stopped taking Ritalin. (My reasons for quitting were visual hallucinations & heart palpitations). I don’t believe I had rhabdo, but I’m certain that the Ritalin was the cause of my body pain.]

We are in agreement with those who have been discussing the possibility of mitochondrial myopathy. Exacerbation of symptoms after physical exertion or exposure to mitochondrial toxins is consistent with skeletal muscle mitochondrial dysfunction. No other condition matches the clinical picture this well. While we like the idea of CPT II deficiency, it is only one of the many possible forms of mitochondrial myopathy.

This is a problem of differential diagnosis. Simplistically, she either has (a) a defined diagnosis or (b) one not previously defined. In order to uncover which category she falls into, and if (a) which label applies, all medical records deemed possibly related to her problem should be provided. Ideally, this would include a family history, environmental and occupational exposures and a review of systems. If if I read this article correctly, the only clinical data provided is from an acute admission, and the records from her evaluation at a tertiary neuromuscular disease center are not. From the limited data provided, it isn’t clear to me if she has had an extensive metabolic or genomic assessment, although disorders in both these categories have been suggested. It isn’t stated what muscle biopsy evaluations were performed, nor the detailed findings. Steve Rinsler, MD

I hope you'll do the same thing with other unsolved illnesses -- for example, this one mentioned in the Times: https://well.blogs.nytimes.com/2016/06/13/dizzy-and-disoriented-with-no-...

I am not a medical professional, but I wondered about the seizure the patient reported. Can seizures occur in a particular set of nerves such as those controlling the symptomatic muscles? The increasing frequency strikes me as a cue to look for something in the particular nerve and muscle system or to consider whether a neural pathway has been created. Is there something interesting in nature of activity that preceded the symptoms? Another possibility might be absence of hydration or inadequate nutrition. How does the body notify us of its needs for water or nutrients? Is the patient overly concerned about her weight or ‘too busy’ to grab a pre-hike meal or to take water for hydration. Could the other pains be a more generated seizure or unrelated (eg, arthritic) in origin?

Carnitine palmitoyltransferase II deficiency, myopathic form. To make the diagnosis, one can look at CPT enzyme activity in muscle or do molecular genetic testing. She can do some dietary modification, eating high-carbohydrate diet (70%) and low fat (<20%) and avoid a fasting state and prolonged exercise. Since this is autosomal recessive inheritance, it would be a good idea to seek referral to genetic counselor.

Ehlers Danlos Syndromes cause hollow organ, skin, and vascular fragility-- and most notably, severe growing pains and myalgia. A myriad of issues arise from EDS: as collagen is our brick and mortar. Its the equivalent of building a house with faulty materials: some problems are quite obvious, but some are structural and unseen.

Has anyone considered HIV? There have been case studies of non-traumatic rhabdo associated with HIV. This could explain why her symptoms came on directly following a viral illness. HIV could also have caused her seizures as well as some of the abnormalities on her lab tests.

Wow! Very thoughtful, NYTimes!

I can't help, but I'm glad this young woman's illness is being treated seriously. I worked in the hospital industry long enough to know that when someone looks as 'perfect' as she does, real illness can be dismissed as psychiatric.

I would consider hypokalemic periodic paralysis. Her potassium levels were modestly low upon each acute (ER) presentation. This was one of the consistent findings not related to a consequence of the rhabdo (in rhabdo otherwise would expect elevations in potassium which would start to offset initial low K). Though potassium levels are usually dramatically lower, some cases are reported to exhibit a decrease from baseline even remaining within the normal range. Rest after exercise upon one circumstance, family history with partial penetrance in her mother, age of onset, exacerbation with infection, can awaken from sleep, can be associated with pain and rhabdo with certain mutation.

Are the Seizures causing the Rhabdo, or vice-versa ??? How long did she actually take anti-seizure medication, and did she have any rhabdo symptoms during THAT period ??? Has she had any witnessed seizures, versus those that occur occur during sleep ???

I'm wondering about sickle cell disease. Run a hemoglobin electrophoresis.

Regarding my previous comment on antibiotic toxicity, fluoroquinolone-class antibiotics affect the central nervous system, which could account for the seizure. Their negative effects persist, and some effects can also not appear until some days, weeks, or months . They include Cipro, Levaquinn, Avelox, their generics. Angela's history doesn't name that first abx (2008). From my personal experience of rhabdo following activity only a little more strenuous than normal, I see Angel's reactions as possibly caused by FQ exposure in 2008. I am presently in a rehab center working to recover from a big rhabdo event that happened three months ago, that almost took my life. I have lived with fluoroquinolone toxicity effects for almost 20 years. It was only in the past year that I started to understand what was causing my symptoms, including rhabdo. I'm in the process of learning how to manage this. Many doctors don't acknowledge that fluoroquinolone toxicity exists, even though the FDA has now given it a name (FQAD), and has Black Box warnings on all FQ's starting from 2008, with the most recent update in 2016.

The recurrent muscle pains seem like sickle cell disease. Run a hemoglobin electrophoresis.

Does she live with that Dog, or any other pets??? For how long ? How is the health of any animals in the household ? Do THEY receive medications or treatment for Fleas or other parasites ???

What is the point of this exercise? Why can't this be done through comments as it was previously done. People previously replied to other respondents. And gave their reasoning for how they came up with the diagnosis. There used to e so many comments and interesting reasoning what happened. Now I guess only those doing the interactive exercise can see the outcome? Why the extra layers of giving e'mail address and information where you live?

A unique feature in the approach in homeopathy is to treat the totality of symptoms as one integrated profile and then to find a medicine whose effects matches that profile in totality. One advantage to this approach is that one can still treat, even cure, without necessarily coming to a conclusion about the diagnosis. This is such a case that could be helped by homeopathy and natural medicine. This reader analyzed the few, albeit incomplete, symptoms presented in the video, and its very possible homeopathy could help, as some homeopathic medicines appear to match the profile. Why not give it a try while waiting for conventional medicine to find a cure? Without trying to be presumptuous, this reader, as a professional, would like to offer free treatment. Or if the patient prefers to pay something, she may donate the fee to charity.

I agree with seeing a genetics expert, but I also think she should see an endocrinologist with a specialty in metabolic diseases. This in my country, would likely be found at at a tertiary care teaching hospital, as would a genetics specialist. She should have a muscle biopsy while she is having an attack of rhabdo. It seems most likely that she has a metabolic disorder of either fatty acid metabolism, or a glucose/glycogen metabolic disorder. I am not a doctor, so I am unaware of other testing that should be done, although I am sure there must be some way of testing glycogen levels with exercise.

She's not taking statins, by any chance, is she? Rhabdo is a known side-effect of statins.

Anyone looking at antibiotic adverse effects that are persistent, and are often delayed as well? Fluoroquinolones is a class of antibiotics that do this. I've experienced rhabdo due to FQ toxicity. FQ's produce damage to mitochondrial DNA, as well as affect collagen production, & cell healing & energy. I have had rhabdo from minor episodes of repetitive movement. I've sometimes lost the ability to walk, & more grievous experiences. if Angela's abx was an FQ, nutrition & very careful movement therapy, with way more than normal amounts of rest, can reverse some of the negative effects. At the least, if heavy activity causes rhabdo over & over, dial the activity down to give tissues more chance to rebuild, & understand that light to moderate activity plus LOTS of rest is how to care for the vulnerable body here.

My (amateur) guess was also carnitine palmitoyltransferase II deficiency. I thought it was interesting that the patient had had recent infections preceding several of her episodes, and I read infection could be a trigger, in addition to exercise. I think cold weather can also be a trigger, but I believe the patient lived in Las Vegas, so maybe she is not exposed to that particular trigger.

While this history does not exactly fit the diagnosis and there are questions I have about her symptoms and the timing of the episodes, one thing I thought of was acute intermittent porphyria. There are some variations of the classic presentation, but I wonder if porphyrin levels were done?

I'm a genetics trainee in Boston. I submitted a comment to the earlier version of this article. To me, the most unsettling mystery of the case is that Angel was not referred to a medical geneticist or biochemical geneticist (also known as a metabolism specialist) during the many years she experienced recurrent rhabdomyolysis. Recurrent rhabdomyolysis is an indication for a referral to a genetics clinic. Some clinicians may not be familiar with the field of medical genetics, however, or may not consider that a genetic diagnosis can change long-term patient outcomes. In Angel's case, a referral to a geneticist or a metabolism specialist may have spared her from a muscle biopsy, brain MRI, the emotional toll of her diagnostic odyssey — and given her actionable ways to treat and avoid future episodes of recurrent rhabdomyolysis. You mention that many commenters worked alone, but I actually posted this case on a Facebook group that includes over 130 female genetics and metabolism specialists from around the world. We agreed that several metabolic disorders (rare genetic disorders of energy production) need to be evaluated. At the top of the list is carnitine palmitoyltransferase II deficiency. Also possible are mutations in the genes LPIN1, RYR1, and the disorder myoadenylate deaminase deficiency. A fatty acid oxidation disorder is possible but less likely. The first step is to send an acylcarnitine profile, ideally in the setting of rhabdomyolysis.

I wondered at the time why commenters weren't allowed to discuss things with each other. I think this is a good decision. I don't have any good ideas for Angel but hope that others do and mention them here.