Unraveling the Genetic puzzle: MTRR Mutation and Autism Spectrum Disorder

Unraveling the Genetic puzzle: MTRR Mutation and Autism Spectrum Disorder

MTRR and autism link

Autism Spectrum Disorder (ASD) presents as a complex neurodevelopmental challenge impacting countless lives globally. While its roots remain enigmatic, genetic facets emerge as pivotal contributors. Within this intricate genetic panorama, the MTRR gene mutation emerges as a potential piece in autism’s intricate puzzle.

This article navigates the connection between MTRR mutations and autism, venturing into genetics’ profound influence on neurodevelopment.

Decoding MTRR's Methylation Role

MTRR—5-methyltetrahydrofolate-homocysteine methyltransferase reductase—resides at the core of the folate-methionine cycle. This pathway oversees homocysteine levels, nourishing DNA synthesis and methylation reactions. Methylation, an epigenetic feat, grafts methyl groups onto DNA, steering gene expression sans genetic alteration. Hence, MTRR orchestrates DNA methylation patterns, pivotal for regular neurodevelopment and cerebral function.

The Nexus: MTRR Mutation and Autism

Recent insights highlight the intertwinement of MTRR gene mutations and autism risk. Specific MTRR gene deviations can stifle functionality, upending the folate-methionine cycle and perturbing DNA methylation. Autism-affected individuals often bear distinct MTRR mutations or perturbations in gene expression.

Neurodevelopment's Impacted Canvas

MTRR’s discordance casts far-reaching shadows over neurodevelopment. Methylation rules supreme during cerebral maturation, guiding genes entwined with synaptic plasticity, neural interconnectivity, and neurotransmitter modulation. Any DNA methylation disruption, courtesy of MTRR mutations, may forge altered cerebral development, potentially fostering autism-linked manifestations.

Symphony of Genes and Environment

Autism’s orchestration involves more than genetics. Genetic susceptibility dances with environmental influences, crafting ASD’s multifaceted tale. Prenatal nutrition, toxin exposure, and maternal well-being partner with genetic glitches, like MTRR variations, possibly amplifying or alleviating autism risk’s impact.

Diagnostic and Therapeutic Horizons

The burgeoning MTRR-autism liaison unfurls avenues for diagnosis and treatment. MTRR variant genetic assays can illumine autism predisposition. Swift identification promises tailored interventions, optimizing neurodevelopmental trajectories for those impacted.

Moreover, comprehending MTRR’s DNA methylation and neurodevelopmental involvement charts the course for targeted therapies. Explorations into recalibrating DNA methylation patterns hold the potential to mitigate MTRR mutation’s impact on autism-linked symptoms.

The Odyssey Ahead: Challenges and Prospects

Promising as it is, the MTRR-autism connection confronts hurdles. Autism’s genetic framework is intricate, an ensemble of genes and interactions. The MTRR-autism interplay bows to a medley of genetic, epigenetic, and environmental nuances.

As science’s quest to decipher autism progresses, resolute inquiry and open thought are vital. Geneticists, neuroscientists, and clinicians’ synergy propels autism comprehension, translating revelations into real benefits for individuals and families.

Conclusion

MTRR mutation’s exploration alongside autism brims with promise, an expedition into uncharted autism dimensions. It accentuates the confluence of genetics, epigenetics, and neurodevelopment, enlightening the labyrinthine nature of this neurodevelopmental enigma. Our march towards enlightenment inches us closer to plumbing autism’s genetic depths and potential interventions, promising solace to those traversing this intricate journey.

Unraveling the Genetics of Autism: The Epigenetic Connection

Unraveling the Genetics of Autism: The Epigenetic Connection

MTHFR and autism

Autism Spectrum Disorder (ASD) remains a complex and enigmatic condition that has intrigued researchers for decades. Understanding the genetic basis of autism is crucial for advancing our knowledge and developing effective treatments. In this article, we delve into a groundbreaking study conducted over five years ago, which shed light on the connection between a specific gene involved in epigenetics and autism.

As we embark on this journey, it’s important to bear in mind that scientific research is continually evolving, and findings from older studies may have been reevaluated since their original publication.

The Epigenetic Link: MTHFR and Autism

In November, a study published in The Journal of Autism and Developmental Disorders revealed intriguing insights into the genetic landscape of autism. The focus was on the gene MTHFR, which plays a crucial role in methylation – an essential epigenetic mechanism that can modify gene expression without altering the DNA sequence.

Epigenetics is a fascinating field that has illuminated how environmental factors can interact with genetics, influencing an individual’s health and development. Methylation involves the addition of methyl groups to DNA, affecting how genes are expressed and regulated. The researchers observed that individuals with autism from simplex families, where only one child is affected, showed a significant association with variants of the MTHFR gene that reduce its enzymatic activity.

MTHFR Variants and Autism Risk

The study revealed two specific variants of the MTHFR gene – 677T and 1298A – as being more prevalent in individuals with autism. These variants each represent a single DNA base change, and carriers of one or both of these variants were more likely to have autism. The significance of this association was observed exclusively in simplex families, whereas multiplex families, with more than one child affected by autism, did not exhibit the same correlation.

Distinguishing Simplex and Multiplex Families

The differentiation between simplex and multiplex families is critical in understanding the genetic factors that contribute to autism risk. Simplex families have a single child affected by autism, and the observed association with MTHFR variants suggests a potential link between these variants and the risk of developing autism in such cases. On the other hand, multiplex families, while showing a higher frequency of inherited autism-linked mutations, did not exhibit the same MTHFR association.

Epigenetics and Autism Risk Heterogeneity

One of the most intriguing aspects of this study is how epigenetics can account for the varying levels of autism risk among individuals with a similar genetic background. Epigenetic mechanisms, like methylation, can create diverse phenotypes from identical genotypes, providing valuable insights into the complexities of autism etiology. Experiments in mice lacking proteins that bind to methyl groups have even exhibited autism-like symptoms, further supporting the role of epigenetics in autism.

Unraveling the Puzzle

This study opened up exciting avenues for further research into the interplay between genetics, epigenetics, and autism risk. Subsequent investigations have likely built upon these findings, aiming to validate and extend the understanding of the MTHFR gene’s role in autism. Scientists have been exploring changes in methylation patterns in individuals with autism compared to neurotypical controls to unravel the intricacies of epigenetic regulation in this disorder.

Conclusion

Autism research has come a long way in the past five years, and this study’s findings marked a significant milestone in understanding the genetic and epigenetic factors contributing to autism risk. As we reflect on this research, it is essential to remember that the scientific landscape is ever-evolving, and new discoveries are continuously shaping our understanding of autism spectrum disorder.

By combining knowledge from both older and more recent studies, we move closer to unlocking the mysteries of autism, ultimately leading to improved diagnosis, treatment, and support for individuals and families affected by this condition.

Resources

1. PubMed (https://pubmed.ncbi.nlm.nih.gov/): A comprehensive database of scientific literature primarily focused on medical and life sciences research.
2. Google Scholar (https://scholar.google.com/): A freely accessible search engine that indexes scholarly articles, theses, books, and conference papers across various disciplines.
3. ScienceDirect (https://www.sciencedirect.com/): A platform providing access to a vast collection of scientific articles and journals covering multiple subject areas.
4. Wiley Online Library (https://onlinelibrary.wiley.com/): A collection of scientific and scholarly articles from Wiley publications.
5. SpringerLink (https://link.springer.com/): A platform offering access to scientific journals, books, and conference proceedings published by Springer.

Childhood Apraxia of Speech-Symptoms, treatments, exercises

Childhood Apraxia of Speech-Symptoms, treatments, exercises

auditory processing disorder

Childhood apraxia of speech (CAS) is a neurological disorder that affects an individual’s ability to produce speech sounds accurately and fluently. CAS is caused by difficulty planning and coordinating the muscle movements needed for speech, and is not caused by weakness or paralysis of the muscles used for speech.

Symptoms of CAS may include:

  1. Difficulty producing sounds: Children with CAS may have difficulty producing certain sounds or may not be able to say words or sounds correctly.
  2. Difficulty with the rhythm and flow of speech: Children with CAS may have difficulty with the rhythm and flow of speech, and may have a choppy or halting speech pattern.
  3. Difficulty with language skills: Children with CAS may have difficulty with language skills, such as understanding and using words and sentences.

Treatment of CAS

CAS can affect children of any age and can range in severity. Treatment for CAS typically involves speech therapy, which can help children improve their speech production skills and develop more effective communication strategies. In some cases, medications may be used to help manage specific symptoms of CAS, such as anxiety or hyperactivity. It is important to note that treatment for CAS is typically tailored to the individual’s specific needs and may involve a combination of therapies and interventions. A healthcare professional, such as a speech therapist or psychologist, can help develop an appropriate treatment plan.

Treatment for childhood apraxia of speech (CAS) typically involves speech therapy, which can help children improve their speech production skills and develop more effective communication strategies. The goals of speech therapy for CAS may include:

  1. Improving speech sound production: Speech therapy can help children with CAS learn to produce speech sounds more accurately and fluently. This may involve activities and exercises to help improve muscle control and coordination.
  2. Improving language skills: Speech therapy can also help children with CAS improve their language skills, such as understanding and using words and sentences.
  3. Developing compensatory strategies: Speech therapy can help children with CAS develop compensatory strategies, such as using gestures or visual aids, to help them communicate more effectively.

Here are a few exercises that may be beneficial for a child with Childhood Apraxia of Speech (CAS):

  1. Articulation exercises: Children with CAS often struggle with the physical movements needed to produce speech sounds correctly. Exercises that focus on the muscles of the face and mouth, such as blowing bubbles, blowing through a straw, or blowing up balloons, can help to improve the child’s ability to coordinate the movement of their speech muscles.
  2. Repetition exercises: Children with CAS may benefit from repeating words and phrases to improve their ability to coordinate the movements needed for speech. This can be done by repeating simple words or phrases, such as “mom” or “I want juice,” in isolation or in short phrases or sentences.
  3. Imitation exercises: Children with CAS may benefit from imitating the speech of others. The child can watch or listen to a model speak and then imitate what they hear. This can help to improve the child’s ability to coordinate the movements needed for speech.
  4. Auditory bombardment: The child listen to different words and phrases repeatedly, which exposes them to a wide range of sounds and words, which helps them in their development of speech sounds.
  5. Tactile cueing: Children with CAS may benefit from having a tactile cue to remind them of the correct position of the articulators. This can be done by placing an object such as a popsicle stick in the child’s mouth to remind them of the correct position for speech sounds.
  6. Motor planning exercises: Children with CAS struggle with planning and coordinating the muscle movements required for speech, so exercises that target this area can be helpful. this can be done by asking child to move their body in specific ways while they are saying a word or phrase, such as making big arm movements while saying the word “big” or touching their nose while saying “nose.”
Resources
  • m B-R, SeoH-S, Ku J-M, et al. Silibinininhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast-cells. Inflammation. Research. 2013;62(11):941-950. doi:10.1007/s00011-013-0640-1.
  • ChapowalA. PetasitesStudy Group. Randomisedcontrolled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ 2002;324:144-6.
  • Hayes, N. A. and Foreman, J. C. The activity of compounds extracted from feverfew on histamine release from rat mast-cells. J Pharm Pharmacol1987;39(6):466-470
  • Hsieh et al. Baicalein inhibits IL-1ß- and TNF-a-induced inflammatory cytokine production from human mast-cells via regulation of the NF-?B pathway. ClinMolAllergy. 5: 5. 2007.
  • TheoharidesTC, Patra P, Boucher W, et al. Chondroitin sulphateinhibits connective tissue mast-cells. British Journal of Pharmacology. 2000;131(6):1039-1049. doi:10.1038/ sj.bjp.0703672.
  • Ro JY, Lee BC, Kim JY, et al. Inhibitory mechanism of aloe single component (alprogen) on mediator release in guinea pig lung mast-cells activated with specific antigenantibodyreactions. J PharmacolExpTher. 2000;292:114–121. 73.
  • https://www.ncbi.nlm.nih.gov/pubmed/24477254
  • https://www.ncbi.nlm.nih.gov/pubmed/28458279
  • https://www.ncbi.nlm.nih.gov/pubmed/9421440
  • https://www.ncbi.nlm.nih.gov/pubmed/10344773
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315779/
Genetic disorders and Autism

Genetic disorders and Autism

possible cause of asd

Many researchers believe that the primary cause of autism are probably genetic disorders. However, it is not possible to find common ground among autistic children living with different genetic diseases. In fact, many known genetic syndromes can have a profound impact on a child’s development and also cause autism similar symptoms, but most children with autism do not have these main genetic disorders.

Here’s a brief explanation of the genetic/neurological conditions that are so far known to result in symptoms of autism:

Fragile X syndrome

This is the most commonly known genetic cause of developmental delay. It has an extremely rare occurrence. The symptoms of Fragile X are quite indistinguishable from autism, although children with Fragile X are more likely to be hyperactive and anxious. Unfortunately, Fragile X usually causes mental impairment, so these children will have to face more challenges in the coming years (most autistic children have a normal mental functions). Fortunately, the vast majority of children with autism have normal X chromosomes.

Fragile X is transmitted by the mother, so the presence of autism, or mental impairment on the mother’s side, would make this diagnosis more likely.              

Rett syndrome

The defect in the X chromosome is responsible for this genetic disorder. However, this affects only girls, because boy fetuses with this defect, as a rule, do not survive. Girls with Rett usually look completely normal, develop normally for several months or even years, and then regress. Characteristic hand-squeezing movements appear, as well as other “neuromuscular problems, such as unsteady walking, tremors, and muscle spasms.

Angelman syndrome

This disease is due to a defect in the UBE3A gene. It leads to severe mental retardation, seizures, and spasmodic muscles. Its symptoms are a happy facial expression, unusual laughter and symptoms characteristic of autism

Neurocutaneous disorders

These genetic-based disorders cause the growth of benign tumors in the brain and skin.  The two most common are: neurofibromatosis (NF) and tuberous sclerosis (TS). The development of the baby with these disorders usually begins normally.  However, when benign tumors begin to grow in the brain, they cause intellectual developmental delays, the child shows psychiatric symptoms, symptoms of autism and may also have seizures. Multiple cream-colored flat spots appear on the skin in the case of NF, or leaf-shaped white spots in the case of TS. A genetic examination and a CT or MRI scan of the brain can provide a diagnosis. 

Chromosome mutation 16P11.2

Children with 16p11. 2 deletion syndrome usually have developmental delay and intellectual disability. Characteristics of deletion syndrome include delayed development; intellectual disability; and autism spectrum disorder, which affects communication and social interaction, impaired communication and socialization skills, as well as delayed development of speech and language. This mutation has been found in some children with autism.                  

Bannayan-Riley-Ruvalcaba syndrome

This extreme disease occurs infrequently. It has been found in very few children with autism. It causes a very large head, increased body size, hemangiomas and small cysts form on the skin.     

Smith-Lemli-Opitz syndrome

This disorder develops due to a metabolic defect in cholesterol production. These children usually have a fusion of second and third toes, are characterized by disparate facial features, such as drooping eyelids, small and low-seated ears, or split uvula, small head size and characterized by slow growth.  

Fetal alcohol syndrome

This happens when a pregnant woman drinks alcohol as a way of life, which has consequences for the developing nervous system of the fetus. These babies are retarded in development and show different characteristics of autism, especially hyperactivity. They have a characteristic appearance: the groove between the nose and the upper lip, the so-called philtrum, is flat: the upper lip is thin: the eyes are close to each other. The diagnosis is based on known alcohol exposure.

Landau-Kleffner syndrome

The main feature of this syndrome is the development of seizures from the age of three to seven years, as well as language regression. It differs from autism in that social skills usually remain normal, and the loss of language ability occurs much later than in autism.

Although the last two are not genetic diseases, it is also up to a neurologist to determine their presence, as in the case of the other disorders mentioned above.

What remains a question for researchers is whether there is a single underlying genetic cause of autism. No genetic disease has been identified that is present in all children with autism, and is expected to be less and less likely to do so. In fact, it is important to screen for genetic diseases in order to identify the genetic risk in infants and to start treatment and development as early as possible.

Resources
  • m B-R, SeoH-S, Ku J-M, et al. Silibinininhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast-cells. Inflammation. Research. 2013;62(11):941-950. doi:10.1007/s00011-013-0640-1.
  • ChapowalA. PetasitesStudy Group. Randomisedcontrolled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ 2002;324:144-6.
  • Hayes, N. A. and Foreman, J. C. The activity of compounds extracted from feverfew on histamine release from rat mast-cells. J Pharm Pharmacol1987;39(6):466-470
  • Hsieh et al. Baicalein inhibits IL-1ß- and TNF-a-induced inflammatory cytokine production from human mast-cells via regulation of the NF-?B pathway. ClinMolAllergy. 5: 5. 2007.
  • TheoharidesTC, Patra P, Boucher W, et al. Chondroitin sulphateinhibits connective tissue mast-cells. British Journal of Pharmacology. 2000;131(6):1039-1049. doi:10.1038/ sj.bjp.0703672.
  • Ro JY, Lee BC, Kim JY, et al. Inhibitory mechanism of aloe single component (alprogen) on mediator release in guinea pig lung mast-cells activated with specific antigenantibodyreactions. J PharmacolExpTher. 2000;292:114–121. 73.
  • https://www.ncbi.nlm.nih.gov/pubmed/24477254
  • https://www.ncbi.nlm.nih.gov/pubmed/28458279
  • https://www.ncbi.nlm.nih.gov/pubmed/9421440
  • https://www.ncbi.nlm.nih.gov/pubmed/10344773
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315779/
Possible causes of Autism

Possible causes of Autism

causes of asd

As parents, we are very shocked when it turns out that our child is not developing properly and finally receives the diagnosis. We as a parent would try everything that shows promise, just to help our child. Why we? We are trying to find a possible cause of autism, but this medical problem is very complex and difficult to find the exact cause, but there are a few possibilities to start

AUTISM is a very complicated condition that can have many causes, and precisely because it can cause autistic symptoms, it is terribly difficult to find a solution to it. Because what works for one child is not the cause of their symptoms for another, only the symptoms are similar.

What are the possible causes of autism

The exact cause of autism is not fully understood, and it is likely that there are multiple factors that contribute to the development of the disorder. Research has shown that both genetic and environmental factors may play a role in the development of autism.

Genetic factors:

Many studies have found that people with autism are more likely to have certain genetic variations or mutations. These genetic changes may be inherited from a person’s parents or may occur spontaneously during fetal development. It is thought that the combination of multiple genetic changes may contribute to the development of autism.

Environmental factors:

Research has also identified a number of environmental factors that may increase the risk of developing autism. These include prenatal exposure to certain medications, infections, and toxins; premature birth; and certain medical conditions that occur during pregnancy or childbirth. However, it is important to note that most people with these risk factors do not develop autism, and that the majority of cases of autism do not have a known cause.

Autism can be an associated medical state of certain genetic diseases which can be a more severe genetic disease or “just” a genetically determined methylation problem.

There are so-called biomedical theories regarding the causes of autism. Examples include:

Exposure to toxic chemicals

In our modern society, we are exposed to many hazardous chemicals. Air and water are becoming increasingly polluted, heavy metals can get into our bodies from toys, food and, water, etc., we come into contact with toxic chemicals every day, which are added to household accessories and furniture, but they are also found in pesticides and food.

We know that metals like lead and mercury can damage brain tissue. We know that various body organs can be damaged by chemicals, causing metabolic and hormonal imbalances. In fact, the immune system can also be affected by these heavy metals, leaving the body more open to various degenerative states. It is possible that these exposures add up, and some babies simply cannot handle this load, which begins already in the womb and continues throughout childhood.

In 2004, an Environmental Working Group examined the umbilical cord blood of ten randomly selected mothers and found a staggering amount of chemicals and pollutants. Tests revealed 287 different toxic chemicals, including mercury, pesticides, and other chemicals (Source: https://www.ewg.org/research/body-burden-pollution-newborns)

Most of the chemicals found are known to cause cancer, mutations, and birth defects. The study showed that the question is not whether unborn babies are exposed to toxins but how exposed they are to poisons and how they are affected by such amounts of poison.

The developing nervous system of the infant (which usually happens from conception to the age of three) is particularly susceptible to damage caused by such exposures. When a brain cell is damaged, so are the dozens of nerve pathways that connect the cells. If, for example, the area of the brain that regulates language development is damaged by thousands of nerve cells, then the child’s speech development and comprehension will be delayed, or his speech will simply be incomprehensible. Depending on the rate of injury.

Many environmental toxic substances – including mercury, lead, arsenic, and toluene – cause neurodevelopmental disorders such as autism, cerebral palsy, ADHD, and mental retardation. This may be due to the fact that the developing brain is more sensitive to injuries caused by toxic substances than the adult brain. https://www.psychiatrictimes.com/view/environmental-toxicants-and-autism-spectrum-disorder

Autism is a multifactorial neurodevelopmental disorder caused by genetic and environmental factors.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377970/

According to the latest evidence,  up to 40-50% of autism spectrum disorder (ASD) can be determined by environmental factors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356236/

Although the role of genetic disorders in autism spectrum disorder (ASD) is accepted as a fact, recent studies point to an equal contribution of environmental factors, especially environmental toxic substances. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944636/

It is not yet possible to know exactly what environmental toxins contribute to autism. Prevention is of paramount importance since the elimination of toxins is a very difficult task. It is very important to limit the exposure of the expectant mother and baby.

It is worth learning how best to remove those chemicals from the vicinity of our children. Download the most common toxin deposits here

However, the theory of chemical exposure does not answer the question of why autism occurs in some children but not in others. This is just the only element of the puzzle. The answer to this should be sought in the child’s genetics, his methylation state! There we find the answer to the question of why environmental toxins can cause neurological symptoms in one child and not in another. This can help us understand why autism is a spectrum in which children show different symptoms and are affected with varying degrees of severity.

Studies have shown that children with autism have significantly higher heavy metal loads. Likely, detoxification processes and cell regeneration do not work properly in children with autism, and this can be caused by methylation disorder.

You can find articles on methylation here: Methylation and Autism

List of other probabile cause of Autism

If you want to read more about the possible causes, just click the name of the causes below:

 

  • Genetic problems
  • Differences in brain structure in autism
  • Prenatal and birth factors
  • Theory based on disorders of mitochondria
  • Methylation disorders
Resources
  • m B-R, SeoH-S, Ku J-M, et al. Silibinininhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast-cells. Inflammation. Research. 2013;62(11):941-950. doi:10.1007/s00011-013-0640-1.
  • ChapowalA. PetasitesStudy Group. Randomisedcontrolled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ 2002;324:144-6.
  • Hayes, N. A. and Foreman, J. C. The activity of compounds extracted from feverfew on histamine release from rat mast-cells. J Pharm Pharmacol1987;39(6):466-470
  • Hsieh et al. Baicalein inhibits IL-1ß- and TNF-a-induced inflammatory cytokine production from human mast-cells via regulation of the NF-?B pathway. ClinMolAllergy. 5: 5. 2007.
  • TheoharidesTC, Patra P, Boucher W, et al. Chondroitin sulphateinhibits connective tissue mast-cells. British Journal of Pharmacology. 2000;131(6):1039-1049. doi:10.1038/ sj.bjp.0703672.
  • Ro JY, Lee BC, Kim JY, et al. Inhibitory mechanism of aloe single component (alprogen) on mediator release in guinea pig lung mast-cells activated with specific antigenantibodyreactions. J PharmacolExpTher. 2000;292:114–121. 73.
  • https://www.ncbi.nlm.nih.gov/pubmed/24477254
  • https://www.ncbi.nlm.nih.gov/pubmed/28458279
  • https://www.ncbi.nlm.nih.gov/pubmed/9421440
  • https://www.ncbi.nlm.nih.gov/pubmed/10344773
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315779/