Over the course of Aislinn’s life, a lot of energy has been spent talking to her specialists at Children’s Hospital Colorado and primary care pediatricians.  Some questions were answered but more were left dangling.   The common thread was always “we don’t know” and “science needs a chance to develop” and “she is a medical mystery”.  Ugh in other words, current testing had been exhausted which left a tie with science.  Excitingly, the tie began to tip in Aislinn’s favor in the last four months!   After seven years and seven months of research, newer science is revealing some answers regarding Aislinn’s condition and HOPE is prevailing. 

 

Two key things have recently come out that are significant in learning and understanding her overall condition.  They are a discovery of very low iron stores through a Ferritin test and a gene mutation found in the results of her whole exome sequencing test (extensive DNA testing).  During the last few months, Aislinn’s iron stores have been coming up slowly using an iron supplement in her daily feeds which has helped reduce bruising, restless legs, and added a bit of energy to her day.   However with great excitement, I am about to share the results of Aislinn’s whole exome sequencing test.    

 

In a meeting with the genetics team at Children’s Hospital Colorado, we learned Aislinn has a gene mutation involving a broad category that doctors sometimes refer to as “channelopathies” - meaning diseases of ion channels in neurons, of which the N-methyl-D-aspartate receptors (NMDA) receptor is one.   Channelopathies are diseases caused by disturbed function of ion channel subunits or the proteins that regulate them.[1]  Glutamate receptor, ionotropic, N-methyl D-aspartate 1 or GRIN1 is a protein-coding gene and is a subunit of NMDA.   GRIN1 and other subunits have an important part in the plasticity of synapses, which is believed to underlie memory and learning.  Aislinn’s specific mutation is in GRIN1 and is not present in me or her daddy. Deep stuff, right? 

 

So what does a GRIN1 mutation mean for Aislinn?  It means she is one of three known cases with a GRIN1 mutation whom are similarly situated.  It’s probable that it is the cause for her intellectual disability, global seizures, sleep difficulties, tachycardia, sinus tachycardia, dysmotility, and hypotonia.  It involves careful consideration of medicine dosages due to her ability to metabolize them.  It causes the need for more research of which she will be a part of through the University of Colorado Denver and Emory University School of Medicine.  It signifies hope because there is a movement to create medicines/treatments based on gene mutations to help mitigate physical and intellectual deterioration.

 

At last, I am able to drop the dreaded baggage of guilt that her condition is not tied to something I did or did not do during my pregnancy with her.  Hooray! I did not realize the how much the baggage weighted down my spirit and tugged at my smile.  With a spring in my step and song in my head, I am free to conitnue trailblazing! Once again I am able to GRIN from the inside out!     

 

Much love,

Michelle D. Shelley, APA (Mom to seven and ½ year old Aislinn with a GRIN1 mutation and unspecified Mitochondrial disease)

 

For more information on a case study used to explain Aislinn’s GRIN1 mutation, please read  Excess of De Novo Deleterious Mutations in Genes Associated with Glutamatergic Systems in Nonsyndromic Intellectual Disability from The American Journal of human Genetics.

 

 

 

References

^ Robert S. Kass (2005). "The channelopathies: novel insights into molecular and genetic mechanisms of human disease". Journal of Clinical Investigation 115 (8): 1986–9. doi:10.1172/JCI26011. PMC 1180558. PMID 16075038