ResearchSpeak: what have the leukodystrophies and MS in common?

I wonder how many PPMSers have been misdiagnosed? #ResearchSpeak #MSBlog #MSResearch

“When I was still a ‘junior neurology consultant’ I made a spot diagnosis over the telephone that may have been life saving. One the lab technicians phoned me for advice. Her aunt who was in early 50’s with a diagnosis of PPMS and been admitted to her local hospital in ‘shock’ with a very low blood pressure and low glucose level and was in intensive care and not doing well. She was asking me for advice. This lady had presented in her 40’s with a progressive spastic paraparesis and was investigated and diagnosed as having PPMS. When I heard the story I suggested the medical team make sure she did not have Addison’s disease (adrenal failure) and if she did the diagnosis of PPMS may be wrong; I suggested she could have adrenomyeloneuropathy (AMN) and adrenal failure. It turns out I was right and the diagnosis of PPMS was wrong. Don’t be surprised this is not an uncommon mistake. AMN is a relatively rare inborn error of metabolism due to faulty, or mutated, gene located on the X-chromosome. The gene is called ABCD1 and encodes for the so called peroxisomal membrane transporter which is responsible for transporting very long chain fatty acids into the an organelle called the peroxisomes for degradation. Mutations in this gene that interfere with this process, damage the myelin, and cause AMN. We usually make the diagnosis by screening the blood for long-chain fatty acid levels (raised) and checking peripheral nerve conduction studies (slow conduction due to faulty myelin). In general I don’t make a diagnosis of PPMS without a battery of tests that includes these two tests.”

“As the ABCD1 gene is on the X-chromosome it has a different manifestation in males and typically causes adrenoleukodystrophy (ADL), a devastating white matter disease of males. ADL is interesting in that it has an inflammatory variant that has many imaging and pathological features similar to MS, including the presence of locally synthesised oligoclonal IgG bands (OCBs) in the spinal fluid. How the hell does a genetic disorder trigger focal inflammation in little boys that looks very similar to MS, but cause a more indolent delayed neurodegenerative disease in adult female carrier? Answer this question and we may be able to find the cause of MS. In addition to ADL/AMN, many of the other leukodystrophies (white matter dystrophies) have similarities to MS. Can those of us who work in the field of MS learn from those researchers and clinicians working in the leukodystrophy field, and vice versa? Yes, I am sure we can. To address this cross-fertilization of ideas we are hosting an open UCLP MS & Leukodystrophy meeting at Queen Square. I am giving an overview of the diagnosis of MS and how we define a disease when we don’t know its cause. For the leukodystrophies the definition and diagnosis are usually based on a genetic test. Whatever happens at this meeting it should be good fun and hopefully it will generate some new ideas that may benefit you in the future.”

8 thoughts on “ResearchSpeak: what have the leukodystrophies and MS in common?”

  1. Sadly I know this story and after the brilliant diagnosis, simple treatment and stabilization….unfortunately more mess-ups and the story did not end well.So making diagosis is only the first part of the doctors art…the next bit is providing early effective treatments and keping on top of the situtation. This is why is important to bring into your treatment expectations and treatment goals

  2. How do the MRI scans of MS patients and leukodystrophy patients compare? If they are very similar is this why you think some people diagnosed with PPMS may not in fact have PPMS? When does AMN normally make its presence apparent? Are you suggesting that the blood test for raised long-chain fatty acid levels should be a part of the diagnostic workup if a patient with suspected MS has never had apparent relapses?

  3. Are you talking about PPMS only or just generally all of MS?Is MS were a genetic disorder then what to make of EBV as the cause of MS?A bit confused now by this info……….

    1. In fact from what I understand of what Prof. G. published Leukodystrophy/ Adrenomyeloneuropathy is that they are properly genetic disorder (fisorder in the ABC1 gene), and not the MS. And that AMN and the ADL share very similar symptoms to MS. Why keep these pathophysiological similarities Prof. G believes answer to MS can also be given to deepening of the AMN and the ADL.So the difference between the three diseases is done by genetic testing… From what I see the same confusion occurs between the MS and Neuromyelitis Optics, where the same distinction is made by the anti-aquaporina4 examination…

  4. I watched the documentary The Curious case of the Clark Brothers when I was going through my first relapse. It showed one of the brothers had a dislike to being touched on his arms. It was strange as at the time I was going through a similar thing, my mother put her hand on my shoulder and it was painful. I felt at the time I could really relate to what he was feeling.

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