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In: Neurodevelopment Disorder

Nutritional and Metabolic Gene Status With Autism Versus Neurotypical

Children and the Association with Autism Severity

 

Introduction

Current research demonstrated a strong relationship between the genes that control nutrition and metabolic function that manifest as early childhood developmental disorders. Studies reveal low levels of biotin, plasma glutathione, RBC SAMe, plasma uridine, plasma ATP, RBC NADH, RBC NADPH, CoQ10, plasma sulfate, plasma tryptophan, dopamine, glutathione, high level of oxidative stress markers and plasma glutamate. https://doi.org/10.1186/1743-7075-8-34

 

Genes Implicated

There are many implicated genes in Autism and Neurotypical children that demonstrate possible pathway disturbances that involve key functional proteins and enzymes that control major neurotransmitters, folate metabolism and cofactors that regulate vitamin and mineral metabolism. I have listed some of these genes for review. http://www.genecards.org/Search/Keyword?queryString=autism%20and%20nutrition%20

 

RPS6KA1, ABCB1, PIK3CG, RPS27A, HIF1A, PDXK, SOD2, MUC1, NOS1, SLC1A1, GRIA3, SLC1A3, GRIA1, SLC1A2, SLC11A2, NOS2, NTS, NTRK2, APOE, L1CAM, SST, SERPINA1, SCT, HMGB1, BDNF, RPS6KB1, HMBS, AGRP, SERPINC1, SERTAD3, HMGCR, GHSR, ERBB4, HGF, SOD1, GOPC, MTRR, PCBD1, HFE, HRH1, STX1A, ADCYAP1, MAPK3, EIF4EBP1, HRH2, SLC6A4, LEP, SLC7A5, APP, SLC6A3, PIGW, ACOX1, PIK3CA, SLC19A1, SLC4A4, ALDH5A1, SLC40A1, SLC6A14, GRIA2, ALDH2, BCR, GPX1, GPRC6A, SSTR5, EP300, SETD2, PRKAA1, FLNA, CBS, CALB2, CAT, POU1F1, PSAP, CASK, FLG, IRS1, GH1, MTOR, ITGA4, BTD, GFM1, IL1RN, GNRHR, GHRL, MAP2, CDKN1B, CDKN3, CDX2, PVALB, CD40LG, NR3C1, ATF6, ERBB2, PPIG, PRL, CASP9, CCL17, MC3R, CCK, CASP3, GAD2, PSEN1, MAP1B, PRLR, ADA, MAOB, CALCA, SNCA, MC4R, ACHE, PRKAA2, CCL2, GHR, PRKG2, CD79A, MTR, PTEN, ITGB3, LEPR, DYRK1A, BLZF1, TARDBP, VDR, VCP, IL1RAPL2, IGFBP3, MAPT, TPH1, TTF2, IGF1, CALB1, CARTPT, NGF, C9orf72, CYP2C19, CYP1A2, SQSTM1, PTS, CYP2R1, CYFIP2, CP, CPA1, CYP21A2, ACE, ADRB2, AKT1, PON1, GNAQ, INS, RETN, RFC1, RET, PTK2, REG1B, COMT, CNR1, CREBBP, MDM2, RAB39B, RARB, CDKN2A, OXT, PTGS2, PAH, KCNQ1, KDR, QDPR, PYY, SREBF1, CHAT, REG1A, CHMP2B, HCRT, MECP2, POMC, DRD4, DPYD, CTSC, DAO, DCTN1, DHFR, DPP4, CTNNB1, DRD2, CSN1S1, TH, TLR4, TF, TCN2, ELN, TYMS, ALPP, ACACA, MAG, TYMP, BRCA1, IL2, IL1B, IL5, IL2RB, IL10, VEGFA, GFAP, VIP, IL2RA, XDH, NPY, ASPA, IL12A, MTHFR, FHIT, MKRN3, AR, GSTT1, ADH1C, SMARCA1, ADH1B, GSTM1, TERT, TP53, TNF, IFNA1, TREM2, GDF15, ADIPOQ, GRN, GCH1, SYP, NEFL, LHX3, LDLR, LEPQTL1, MT-ND4, MT-TL1, EXT1, IGFBP2, TSPO, ATRX, MTHFD1, TSC1, GDNF, EFS, FOXP2, HTR2C, BMPR1A, GSTP1, TGFB1, EGF, HTT, TGFA, ADH7, IFNG, TG, TPO, APC, LRP5

The genes listed above involve many system controls including; immune regulation, inflammatory control, thyroid metabolism, folate metabolism, adrenal function, choline metabolism, vitamin B12 metabolism, dopamine pathways, iron utilization, biotin and thiamine cofactor transport and intracellular folate metabolism, electrolyte and gating function, oxidative metabolism and antioxidant defense, vitamin D metabolism, cell energy regulation, glutathione metabolism, histamine mast cell control, acid / base pH balance, serotonin / tryptophan metabolism, glycemic / insulin control, leptin signaling and other important metabolic control genes.

 

There are additional genes that are involved in neuroinflammatory patterns seen in PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) and PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) not listed but can be an addition to any custom panel. GeneSavvy NeuroDevGS has all of the genes above and more as well as the genes implicated in PANS and PANDAS.

 

Conclusion

It is essential to do comprehensive genetic testing (preferably whole exome) to curate all phenotypes associated with these nutritional implications in order to support key functional protein pathways and develop specific actionable treatment.

 

 

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Mitochondria are the energy producers of human cells. The energy currency for the work that is required to power up metabolism by producing the energy-rich molecule adenosine triphosphate (ATP). The ATP is produced in the mitochondria using energy stored in the food that is consumed.

These ATP’s are essential in keeping every step of metabolism in equilibrium which in turn effects every system of the human body including immunity, detoxification, hormones, brain neurotransmitters, etc.

Genetic testing to determine metabolic efficiency in chronic health concerns is essential. Also essential in conditions like OCD, ADHD, ASD (Autism), Fatigue, Immune Related Fatigue, Chronic Infections, etc

Genetic genotyping and phenotyping assist in identifying key characteristics that involve mitochondrial health. Genetic analysis and action can assist in providing answers and remedy for these concerns.

There are hundreds of mitochondria within human cells and it is crucial to protect the mitochondria from age-related stress and oxidative burden in order to prevent functional disease and aging risk. These mitochondria are power generators that are responsible for the cell grid. If they are compromised the functional performance survival of the cell is jeopardized complete loss can result.

Each mitochondria carries its own small circular DNA genome, called mtDNA, the products of which are required for energy production. Because mtDNA has limited repair abilities, normal and mutant versions of mtDNA are often found in the same cell, a condition known as heteroplasmy. Most people start off life with some level of heteroplasmy, and the levels of mutant mtDNA increase throughout life. When a critical threshold level of mutant mtDNA is passed, cells become nonfunctional or die.

When mitochondria mutant mtDNA is critical a process of mitophagy results. The important goal in targeting mitochondria is to prevent it from getting to the point of no return.

It is essential that thorough assessment be made through genetic analysis that specifically assess mtDNA and corresponding gene controls.

Many health conditions are caused by critical mutant mtDNA including neurodegenerative disease, Autism, Autism Spectrum Disorder, Disorders of Autonomic Control, Schizophrenia, Behavioral Disorders like OCD, ADHD, Metabolic and Gating Disturbances, Chronic Immune Functional Related Fatigue, Chronic Pain Syndrome, etc.

GeneSavvy testing is the best form of analysis for these disorders and should be the first place in working up the foundational causes and needed targeting to address the functional disturbances caused by mutant mtDNA and nuclear mitochondrial gene disturbances.

We have analyzed over 2000 genetic results and can affirm that foundational genetic analysis will dramatically inflence treatment targeting and outcomes.

 

http://www.sciencedirect.com/science/article/pii/S0005272815001097

August 8, 2017

Autism and Connectivity

New gene discoveries that code for neuronal connectivity are beginning to give new hope in targeting therapy to address the problems associated with connectivity. The autism spectrum brain exhibits connectivity disturbances that alters communication between neuronal regions. Neuronal mitochondrial depletion is among the causative factors that create impaired connectivity and synaptic control. There are many genes implicated in this phenomenon.

Genes Studied In ASD

http://www.genecards.org/Search/Keyword…

Research Article Links

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691066/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420970/

Autism symptoms can be aggravated by inflammatory activity, chronic sensitivity and neurotransmitter trafficking. There are a variety of combination of therapeutically effective agents in personalized treatment.

Some Guidelines

1. Disodium cromoglycate (Gastrocrom)
‘Mast cell stabilizer’ 100 – 400 mg/day dissolved in water

2. Cyproheptadine (Periactin) Serotonin and histamine-1receptor antagonist
1 – 4 mg/day

3. Ketotifen (Zaditen) Histamine-1receptor antagonist, anti-eosinophil 1 – 4 mg/day

4. Rupatadine (Rupafin) Histamine-1 receptor and platelet activating factor antagonist; mast cell inhibitor, anti-eosinophil 20 mg/day

5. NeuroProtek Contains flavonoids and a proteoglycan Two capsules/20 kg body weight/day and Nrf2 as additional item

6. Black Seed Oil 1 tsp 2x day
7. Autoimmune Paleo Dietary Focus
8. Oxytocin Sublingual cycled (Dopamine)
9. SAMe sublingual cycled (Dopamime)
10. CoQ10 mouth spray
11. NAD+ mouth spray
12. Sublingual biotin and folinate
13. Stem cell therapy as option
14. Hyperbaric therapy
15. Immunotherapy
16. Low Dose Naltrexone

*Doses will vary depending on age and weight of patient.

Other Considerations:
1. Carbohydrate (starch splitting) enzyme repletion
2. Human Breast Milk Derived Probiotic Culture
3. Fecal Implantation healthy donor
4. Antimicrobial eradication in complicated cases

Additional Testing Considerations:
1. Folate Receptor Antibody (FRAT)
www.illiadneuro.com
2. Cunningham Panel (PANS / PANDAS)
http://www.moleculeralabs.com/cunningham-panel-pandas-pans…/