Treatable ID and Some Autism

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).

  

This excellent resource was recently brought to my attention by a reader of this blog from Down Under, another place well worth visiting.  Thanks, Alexandria.

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.

So I am already sold on the idea of some cognitive dysfunction being treatable, but I thought I was in a minority of a few dozen. Apparently not.

A friend recently highlighted my suggested autism therapies to a leading Spanish Neurologist, who clearly thinks I am just dreaming.  What would he make of Sylvia and Clara, the BC Duo?  Too much medicinal marijuana, perhaps? 

Science is all about remaining open-minded.  This should also be true for Medicine, but very often it is not. Combine this with the reality that kids with ID/MR/autism are bottom of the list of most people's priorities and you will see why things do not change, unless YOU make the changes, for your n=1 at home. 

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.

Treatable-ID.org

These are the 81 inborn errors:-

- A -
Aceruloplasminemia
(X-Linked) Adrenoleukodystrophy
AGAT Deficiency
α-Mannosidosis
l.o. Argininemia
l.o. Argininosuccinic Aciduria
Aspartylglucosaminuria

- B -
β-Ketothiolase Deficiency
Biotin Responsive Basal Ganglia Disease
Biotinidase Deficiency

- C -
Cerebral Folate Receptor-α Deficiency
Cerebrotendinous Xanthomatosis
l.o. Citrullinemia
Citrullinemia Type II
Co Enzyme Q10 Deficiency
Cobalamin A Deficiency
Cobalamin B Deficiency
Cobalamin C Deficiency
Cobalamin D Deficiency
Cobalamin E Deficiency
Cobalamin F Deficiency
Cobalamin G Deficiency
Congenital Intrinsic Factor Deficiency
l.o. CPS Deficiency
Creatine Transporter Defect

- D -
DHPR Deficiency (Biopterin Deficiency)

- E -
Ethylmalonic Encephalopathy

- G -
GAMT Deficiency
Gaucher Disease Type III
GLUT1 Deficiency Syndrome
l.o. Glutaric Acidemia I
Glutaric Acidemia II
GTPCH1 Deficiency (Biopterin Deficiency)

- H -
HHH Syndrome:
(Hyperornithinemia, Hyperammonemia, Homocitrullinuria)
HMG-CoA Lyase Deficiency
Holocarboxylase Synthetase Deficiency
Homocystinuria
Hunter Syndrome (MPS II)
Hurler Syndrome (MPS I)
Hyperinsulinism Hyperammonemia Syndrome

- I -
Imerslund Gräsbeck Syndrome
l.o. Isovaleric Acidemia

- M -
Maple Syrup Urine Disease (Variant)
MELAS
Menkes Disease Occipital Horn Syndrome
l.o. Metachromatic Leukodystrophy
3-Methylcrotonylglycinuria
3-Methylglutaconic Aciduria Type I
l.o. Methylmalonic Acidemia
MHBD Deficiency
mHMG-CoA Synthase Deficiency
Molybdenum Cofactor Deficiency Type A
l.o. MTHFR Deficiency

- N - l.o. NAGS Deficiency Niemann Pick Disease Type C l.o. Non-Ketotic Hyperglycinemia - O - l.o. OTC Deficiency - P - PCBD Deficiency (Biopterin Deficiency) PDH Complex Deficiency Phenylketonuria PHGDH Deficiency (Serine deficiency) PSAT Deficiency (Serine deficiency) l.o. Propionic Acidemia PSPH Deficiency (Serine deficiency) PTS Deficiency (Biopterin Deficiency) Pyridoxine Dependent Epilepsy Pyrimidine 5-Nucleotidase Superactivity - S - Sanfilippo Syndrome A (MPS IIIa) Sanfilippo Syndrome B (MPS IIIb) Sanfilippo Syndrome C (MPS IIIc) Sanfilippo Syndrome D (MPS IIId) SCOT Deficiency Sjögren Larsson Syndrome Sly Syndrome (MPS VII) Smith Lemli Opitz Syndrome SPR deficiency (Biopterin deficiency) SSADH Deficiency - T - Thiamine Responsive Encephalopathy Tyrosine Hydroxylase Deficiency Tyrosinemia Type II - W - Wilson Disease

Not to confuse Sylvia and Clara with the other dynamic duo, your kids may know, from DC, rather than BC.

With so many treatable forms of MR/ID/Autism out there, is it not a little strange that thorough metabolic testing and Whole Exome Sequencing (WES) are not standard procedures after diagnosis?

By the way, WES is only as good as its interpretation.  Even world leading centres can be very weak in this respect. Insist on receiving the extended report and check all the possibly dysfunctional genes yourself.  It is not so hard.