Treatable ID/MR

Vancouver is one of the most attractive cities I have visited.  It is home to BC Children’s Hospital and Dr Sylvia Stöckler-Ipsiroglu and Dr Clara van Karnebeek. Together they have produced a remarkably thorough website called Treatable-ID, which sets out information on 82 treatable forms of Intellectual Disability (ID), formerly known as Mental Retardation (MR).

ID/MR and Autism

ID/MR is defined as having an IQ less than 70; this means the cognitively weakest 2.2% of the population.

Classic Autism, Autistic Disorder or what we might now also call Strict Definition Autism affects about 0.3% of the population.  It is likely that about half of this group would score <70 in an IQ test.  I do not suggest they take one.

It is clear that an overlap might exist between the causes of MR/ID and the cause of some Strict Definition Autism.

In earlier posts I have referred to improving cognitive function in autism using Bumetanide.  We even saw that it should also improve cognitive function in Down Syndrome.

I suggested that Diamox/ Acetazolamide, another diuretic, could also have a similar effect (via the AE3 cotransporter).  One reader of this blog, Agnieszka, has been sharing her use of Acetazolamide, in the comments on the previous post.

People with RASopathies often have autism and MR/ID.  There are potential RAS therapies, one of which is a cheap statin drug.

We saw how dendritic spine morphology could be modulated and how that could affect cognitive function.  PAK inhibitors can, in theory, achieve this.

81 inborn errors of metabolism related to Intellectual Disability and amenable to therapy

The BC Duo have collated the data on 81 treatable forms of ID/MR.

Not surprisingly some of these 81 also lead to “autism”, so they must also be treatable.  Roger, one this blog’s followers, has at least one of these 81.

So I suggest that anyone interested in a type of autism with some degree of cognitive impairment takes a good look at their site.

These are the 81 inborn errors:-


  1. Thank you very much for this useful blog. My daughter who is 10 has SCN8A mutation (sodium channels problem) causes her epileptic activity and cognitive impairment/intellectual Disability. She has bilateral epileptic activity and abnormal EEG. She does not have seizures but atopic absence epilepsy.

    She has severe learning difficulties and intellectual disability. She is 10 years old and struggling with learning reading and writing now. She also has speech and articulation problems. She is behind her peers in every area. She has attention deficit disorder and can hardly concentrate on things, which affects her learning. She also has developmental coordination disorder, motor planning and coordination difficulties. She has hypotonia and weak muscles.

    She is immature and has low self-esteem with communication problems. She is shy and needs encouragement.

    She had two MR scan, both clean.

    Heavy Metal urine analysis. High Lead. Used detox supplements: NDF Plus, zeolite, bentonite. Her lead level was 27 four years ago, then after a year it went up to 31, last year it was 15, still over the average range and nickel is above average 23, but our Map dr didn’t think it was important.

    SFS Plus stool analysis. Seems ok.

    Genova MAP test bacterial overgrowth, detox and neurotransmitter issues

    Full Exome Sequence- SCN8A mutation with G1451S variant.

    MTHFR - MTHFR (A1298C) Heterozigiot ve (C6777T) Heterozigiot

    Age (Glucose): Normal
    Glutathion - Normal
    MDA-LDL – High (Cell damage and Oxidative stress)

    Her Lithuim blood test level is another problem. It's less than 0.2. one dr recommended lithuim orarate but the other dr has told us there is no need as the blood tests doesn’t g,ve the real lithium level in the barin he says.

    Regular blood/urine checks and amino acid tests are in the normal range apart from B12 is high 1820 and Folat is over 20.

    I would be grateful if you could advise me.

    Do you have an e-mail account. Is it possible to have consultation from you.

    Many thanks and all the best,

    1. Erin, I am not a doctor so I cannot give consultations.

      I can discuss the science, which might lead you to ask your doctor to make some trials.

      Your gene encodes Nav1.6

      I expect you have read this summary

      SCN8A-Related Epilepsy with Encephalopathy

      This ion channel is expressed in the tiny gaps along the myelin layer (nodes of Ranvier). It contributes to the threshold at which neurons fire. This will create an exicitatory/inhibitory (E/I) imbalance, that is a feature of most autism and some epilepsy.

      This gene is implicated in some multiple sclerosis, which is not a surprise given that Nav1.6 is expressed in the middle of the myelin.

      If myelination is impaired, pro-myelinating therapies might help. Since your daughter does have some motor issues, this is plausible.

      Pro-myelinating therapies include an old Japanese asthma drug called Ibudilast and an old antihistamine called Clemastine. Clemastine was OTC in the US, but is now only available with a prescription as Teva Clemastine 2mg.

      There do seem to be similarities with Dravet Sydrome, as discussed in the above paper. Dravet is caused by SCN1A and SCN2A.

      I see that the standard treatment for SCN8A mutation is to use sodium channel blockers.

      I am not a doctor, but I would think it is worth trying safe interventions that seem to ameliorate the E/I imbalance in Dravet syndrome.

      Professor Catterall did the research on low dose Clonazepam in Dravet Sydrome. The human dose is 0.0006mg/kg once a day. Due to the long half life of Clonazepam, it will take 3 days to reach a stable level and “start working”, if indeed your daughter were to be a responder. This dose is so low it is hard to administer, but the big advantage is that it is not addictive. At typical high doses benzodiazepines are not a good idea.

      Bumetanide also is effective in models of Dravet Syndrome.
      I would suggest you discuss with your doctor making a trial of bumetanide. I would suggest a trial of 2mg once a day for at least a month. You may see an effect after 2 weeks but some responders take longer.

      Many neurological conditions feature oxidative stress, this is easily treated with N-acetyl cysteine. A dose of 600mg 3 or 4 times a day is typical. If your daughter is happy to swallow pills, the "best" NAC seems to be NAC Sustain (it comes as hard tablet so it does not decay before you swallow it).

  2. Thank you so much for your quick reply. I will look into the supplements you wrote and will be searching dravet syndrome and their therapies.

    She takes below supplements;
    Petinimid/Zarontin (Ethosuximide) antiepileptic drug
    Cbd Oil 6 mg in the evenings
    L-Theanin - one capsul in the morning
    Neuro-optimizer - one capsul in the morning
    Bio Pure-Broccoli sprout - one capsul in the evening
    Bio Pure-Cava - one capsul in the evening
    Bio Pure-Brain Tincture (Ginkgo biloba, Rosmarium officinalis, Bacopa monnien) - one capsul in the evening
    Body Bio Cholin
    Pure - Quercetin
    Resveratrol one tea spoon in the evening
    Buffered Vit C
    Cogitum Ampoules- acetylaminosuccinic acid – oen a day for 20 days

    Kentron - uridine-cytidine – (Planning to give one day for three months after cogitum finishes)
    Gliaton Forte – Cholini alfosceras,Acidum (Planning to give one day for three months after cogitum finishes)
    Hopantenic acid - (Planning to give later)
    Berberine - (Planning to give later)
    Buytrat -(Planning to give later)

    What do you think of stem Cell Therapy? I am considering bone marrow sct.

    I would appreciate your reply.

    All the best and many thanks


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