microcephaly

The Lethal Suspects for Microcephaly in Brazil, With Zika Virus at the Bottom of the List

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We often hear that correlation is not causation, so why are world renowned scientists treating the Zika virus as the sole cause of microcephaly in Brazil when there are so many other factors? 

This article was originally published at TheEpochTimes.com and republished with permission. Original posting Here.

Since the virus Zika was blamed for a cluster of cases in northeastern Brazil of the devastating birth defect microcephaly, the mainstream media have been dominated by fear of a Zika pandemic. Meanwhile, the real culprit(s) behind the surge in microcephaly in that corner of Brazil have been ignored, with the exception of a few scientists, and even fewer journalists.

This story started on Feb. 1, 2016, when the World Health Organization (WHO) announced a pandemic emergency with the Zika virus, a much milder cousin of Dengue fever. The WHO blamed Zika alone for the sharp uptick in microcephaly (shrunken heads, resulting in shrunken and undeveloped brains, with a wide range of symptoms and disabilities possible, depending on the severity of the case) in babies born in impoverished areas of northeast Brazil.

Politics and an unscientific approach ensued, with the Centers for Disease Control (CDC) and National Institutes of Health (NIH) joining forces with the WHO. The twin U.S. health care agencies launched a propaganda campaign of fear to justify a money grab from U.S. taxpayers. But for a change, Congress developed a backbone and denied the pleas of President Obama, CDC Director Tom Frieden, and NIHDirector Anthony Fauci, who were seeking $1.9 billion for Zika vaccine R&D.

On June 28, the “Zika Bill” was blocked by Senate Democrats, due to issues over the “provisions of the bill,” but apparently not the lower price tag of $1.1 billion.

Missing CSI Investigation

Whether it’s a failed structure or a broken marriage, it often isn’t one item alone that causes the collapse, but a series of them in a cascade of negative events that does the final damage.

Instead of announcing the Zika pandemic, the three international health agencies should have launched a CSI-type investigation in that quarter of Brazil examining all of the environmental triggers and toxinsthat might be contributing to the surge in microcephaly. But that didn’t happen.

“The increase in microcephaly in that part of the world is unique to Brazil. You don’t see rate increases anywhere else,” Dr. James Lyons-Weiler said in a telephone interview on the likely suspects causing the rise in deformed fetuses and babies.

He explained that the “interactions between two or more of the potential causal factors are rarely ever studied by CDC’s scientists. They are not very good with studying interactions,” which might be the underlying cause of an infectious disease or spread of a virus.

Author and research scientist Lyons-Weiler’s early problem solving skills in recognizing the utility in information in DNA-hybridization led him into deeper research on the evolution of diseases, cancer, and mammals.

In 2015, Dr. Lyons-Weiler launched the Institute for Pure and Applied Knowledge (IPAK), a non-profit organization that since its inception has been challenging half-baked science taken as gospel.

In a co-authored paper that Lyons-Weiler led, his scientific team identified nine likely suspects for the rise in microcephaly. The unpublished paper to date, “Areas of Research and Preliminary Evidence onMicrocephaly, Guillain-Barré Syndrome and Zika Virus Infection in the Western Hemisphere,” outlined the suspects.

They range from “Direct Zika-related microcephaly through unspecified mechanisms” and “molecular mimicry” in two types of vaccines given to pregnant women, to “Glyphosate toxicity in bovine products” leaching into those vaccines, and the unintended outcome of genetically modified (GM) mosquitoes, whose world pilot program was launched in 2012 in that same northeast corner of Brazil by the British concern Oxitec.

“The Zika virus has a protein that matches a human protein within 96 percent. Zika also has an element in its genomic sequence similar to one in other flaviviruses, too, like West Nile to Dengue fever. That means Zika could enter the placenta and blood brain barrier of infants. Yet since there is no increase in acute microcephaly outside of Brazil, if it’s Zika, there may be a missing molecular or chemical co-factor,” Lyons-Weiler explained.

The ability of viruses to produce specific disease symptoms is often known to be modified by co-factors.  “Something is different in Brazil,” said Lyons-Weiler.

Overlooked Glyphosate

On June 1, 2015, Denmark, a farming country, banned the sale and use of Monsanto’s ubiquitous weed killer Roundup, as a result of the Danish Environment Authority declaring glyphosate as a carcinogen. Earlier that year, the WHO classified glyphosate as “probably carcinogenic to humans.”

The ban and the statement had little effect on removing the sale of glyphosate-containing productsin the United States and South America. And that has bugged MIT Senior Research Scientist Stephanie Seneff, Ph.D., who conducts research at the MIT Computer Science and Artificial Intelligence Laboratory.

At this year’s Autism One Conference in Chicago, Dr. Seneff presented a 66-slide deck, “Glyphosate, Folic Acid, Neural Tube Defects and Autism,” highlighting potential associations between chemicals, biology, and children susceptible to autism. In mid-June, Seneff presented at a U.S. Congressional hearing on glyphosate, in Washington, D.C.

In an email, Stephanie Seneff wrote: “It is ridiculous that the only thing the research community seems to be focused on with respect to the microcephaly epidemic in NE Brazil is the Zika virus. While the virus may be a factor in the epidemic, there are many other potential factors that deserve at least equal attention. These include:

(1) “Simultaneous exposure to two herbicides—glufosinate and glyphosate—due to the recent introduction of GMO glufosinate-resistant soybeans on top of the glyphosate-resistant soybeans (glufosinate substitution for glutamine during protein synthesis is a direct path to microcephaly via disruption of asparagine synthase);

(2) “The addition of larvicides directly to the drinking water;

(3) “The introduction of the GM mosquitoes from larvae that were likely fed glyphosate-contaminatedsugar and glyphosate-contaminated blood following maturation;

(4) “The heavy use of ethanol as a fuel in the trucks driving through the region (derived from GM Roundup-ready sugar beets or sugar cane sprayed with Roundup just before harvest), and;

(5) “The recent implementation of policies that encourage vaccination of pregnant women with Tdap, flu vaccine, and possibly MMR vaccine. All of these potential contributors should be thoroughly investigated before concluding that Zika is the entire story with the epidemic.”

What do all of these potential triggers mean? Even if they are not the direct cause of microcephaly, they are contributing to both polluting the land and thus plant, animal, and human life. That should give governments around the world pause.

To date, it has not worked out that way yet.

Where there is big opportunity for billions of dollars in profits, there is Big Industry—Big Pharma, Big Agriculture, Big you name it—led by multinational corporations that seek home run-like profits. There are also big governments that either look the other way or are fine with raking in some of those profits, too.

“The timing is wrong for Zika” said Lyons-Weiler, who pointed to a study showing an increase inmicrocephaly in Brazil two years before Zika made it to Brazil.

“What is clear is the experimentation with whole-cell pertussis vaccination in the slums is ongoing, because the population cannot afford the fee for the clinic, where the safer acellular vaccine is available. The increase in microcephaly began one year after Brazil adopted a mandatory prenatal care program, which includes vaccinations during pregnancy,” he concluded.

Zika is not about science. It’s about money and profit at the expense of the people, domestic and foreign.

Massive New Study Suggests Pesticide the Cause of Microcephaly — NOT Zika Virus

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A new scientific study carried out by the New England Complex Systems Institute (NECSI) is casting doubt on the assumed connection between the Zika virus and microcephaly. The study was prompted by the fact that no similar epidemics of microcephaly are being found in other countries hit hard by the Zika virus.

zika-pesticide

“Recently, the New England Journal of Medicine published the preliminary results of a large study of pregnant Colombian women infected with Zika. Of the nearly 12,000 pregnant women with clinical symptoms of Zika infections until March 28, no cases of microcephaly were reported as of May 2. At the same time, four cases of Zika and microcephaly were reported for women who were symptomless for Zika infections and therefore not included in the study itself.”

The four cases are consistent with the expected normal background rate of microcephaly–2 in 10,000. Also, there have been almost 50 microcephaly cases in Colombia up to April 28 with no connection to the Zika virus.

The mathematical analysis demonstrates that there are at least 60,000 Zika-infected pregnancies in Colombia, yet the near absence of microcephaly calls for a renewed investigation into the cause of this birth defect.

Four days after the NECSI study was reported by media, five new cases of microcephaly with Zika infections were found prior to June 18. However, this is still consistent with the random co-occurrence of each of the separate conditions.

Reports out of Colombia over the next few weeks will provide much more evidence on whether there is a causal connection between Zika virus and microcephaly. If there is a link, the number of microcephaly cases should rise dramatically.

The U.S. Centers for Disease Control and the New England Journal of Medicine (NEJM) have already concluded that Zika is a cause of microcephaly. However, the NEJM acknowledges that no experimental evidence exists yet to support that conclusion. Also, “no flavivirus has ever been shown definitively to cause birth defects in humans, and no reports of adverse pregnancy or birth outcomes were noted during previous outbreaks of Zika virus disease in the Pacific Islands.”

In keeping with the spirit of scientific inquiry, all avenues should remain open in determining the cause of the microcephaly outbreak in Brazil. Evidence could build for the Zika virus link, but scientists are insisting that the insecticide pyriproxyfen should also be explored as a possible cause.

In February we reported that doctors in Brazil and Argentina sounded the alarm over pyriproxyfen, which is used for mosquito control by targeting the larval stage. This chemical was sprayed in the areas most affected by microcephaly, but more significantly, was added to drinking water in the Brazilian state of Pernambuco.

The doctors’ report was widely lambasted in the corporate media, but that has not diminished the possibility of a link between pyriproxyfen and microcephaly. The NECSI, which published the new study on Colombia, has provided a comprehensive review of the facts leading to this hypothesis.

“Pyriproxyfen acts as a larvicide by interfering with the development of mosquito larvae. It may unintentionally do the same in humans. Its structure mimics the role of juvenile hormone, which has been shown to correspond in mammals to a number of molecules including retinoic acid, a metabolite of vitamin A, with which it has cross-reactivity. The application of retinoic acid during development has been shown to cause microcephaly. Methoprene, another juvenile hormone analog that was approved as an insecticide based upon tests performed in the 1970s, has also been shown to bind to the mammalian retinoid X receptor, and to cause developmental disorders in mammals. Isotretinoin is another example of a retinoid causing microcephaly in human babies via maternal exposure and activation of the retinoid X receptor in developing fetuses.”

Pyriproxyfen had never been applied to drinking water on such a scale as it was in Brazil, which began the application in 2014–just before the outbreak of microcephaly. Combined with the fact that other countries with Zika outbreaks are not seeing cases of microcephaly beyond the normal rates of co-occurrence, there is certainly cause for suspicion.

The increase in developmental brain abnormalities following a Zika outbreak in French Polynesia—widely cited by corporate media as proof against the pesticide-microcephaly link—was not a valid comparison due to the much smaller population and relatively few cases. Even the New England Journal of Medicine acknowledged that the French Polynesia case does not provide compelling evidence of Zika being the cause.

Adding another layer of suspicion is the fact that Sumitomo, the Monsanto-linked manufacturer of pyriproxyfen, claimed there is no evidence for developmental toxicity in their product, when in fact a review of their own data found this claim to be false.

Philippe Grandjean, a neurodevelopmental toxicologist affiliated with the Harvard School of Public Health, discovered “an animal test shows possible link to teratogenic effects and smaller skull.” Sumitomo failed to mention their own tests showing “low brain mass and arhinencephaly—incomplete formation of the anterior cerebral hemispheres—in rat pups.”
“Few pesticides have been properly tested for developmental neurotoxicity,” said Grandjean. “This is unfortunate as pesticides are suspected of causing a silent pandemic of neurotoxicity. In this case the absence of proper toxicological data confuses the search for causes of the reported surge in microcephaly.”

While politicians and corporate media continue to ignore the possibility that an insecticide may be causing the microcephaly outbreak in Brazil, continued application of the chemical may be aggravating the problem.

The chemical approach to addressing problems such as mosquitoes is standard procedure for centralized, corporate-backed governments, as it rakes in profits for chemical manufacturers such as Suminoto, which in turn line the pockets of politicians who pushed for the measure.

Viable alternatives are lost in the push for more chemicals. The World Health Organization describes how fish that eat mosquito larvae are an effective part of an integrated biological control program. When El Salvador began putting larvivorous fish in water storage containers, dengue vanished along with the mosquitoes that transmit the disease.

In Guatemala, researchers developed a highly effective mosquito trap called an ovillanta. The device is nothing more than 20-inch cut tire pieces hung in a certain fashion with a pheromone-laden non-toxic solution poured into the bottom, and a piece of floating wood or paper where female mosquitoes are drawn to lay their eggs. Use of the traps prevented new cases of dengue during the entire length of the study.

It is also worth noting that environmental degradation and poverty play a part in mosquito-borne outbreaks such as Zika.

Dino Martins, a Kenyan entomologist, said that “the explosion of mosquitoes in urban areas, which is driving the Zika crisis” is caused by “a lack of natural diversity that would otherwise keep mosquito populations under control, and the proliferation of waste and lack of disposal in some areas which provide artificial habitat for breeding mosquitoes.”

WHO statement on the 2nd meeting of IHR Emergency Committee on Zika virus and observed increase in neurological disorders and neonatal malformations

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The second meeting of the Emergency Committee (EC) convened by the Director-General under the International Health Regulations (2005) (IHR 2005) regarding clusters of microcephaly cases and other neurological disorders in some areas affected by Zika virus was held by teleconference on 8 March 2016, from 13:00 to 16:45 Central European Time.

The WHO Secretariat briefed the Committee on action in implementing the Temporary Recommendations issued by the Director-General on 1 February 2016, and on clusters of microcephaly and Guillain-Barré Syndrome (GBS) that have had a temporal association with Zika virus transmission. The Committee was provided with additional data from observational, comparative and experimental studies on the possible causal association between Zika virus infection, microcephaly and GBS.

The following States Parties provided information on microcephaly, GBS and other neurological disorders occurring in the presence of Zika virus transmission: Brazil, Cabo Verde, Colombia, France, and the United States of America.

The Committee noted the new information from States Parties and academic institutions in terms of case reports, case series, 1 case control study (GBS) and 1 cohort study (microcephaly) on congenital abnormalities and neurologic disease in the presence of Zika virus infection. It reinforced the need for further work to generate additional evidence on this association and to understand any inconsistencies in data from countries. The Committee advised that the clusters of microcephaly cases and other neurological disorders continue to constitute a Public Health Emergency of International Concern (PHEIC), and that there is increasing evidence that there is a causal relationship with Zika virus.

The Committee provided the following advice to the Director-General for her consideration to address the PHEIC, in accordance with IHR (2005).

Microcephaly, other neurological disorders and Zika virus

  • Research into the relationship between new clusters of microcephaly, other neurological disorders, including GBS, and Zika virus, should be intensified.
  • Particular attention should be given to generating additional data on the genetic sequences and clinical effect of different Zika virus strains, studying the neuropathology of microcephaly, conducting additional case-control and cohort studies in other and more recently infected settings, and developing animal models for experimental studies.
  • Research on the natural history of Zika virus infection should be expedited, including on the rates of asymptomatic infection, the implications of asymptomatic infection, particularly with respect to pregnancy, and the persistence of virus excretion.
  • Retrospective and prospective studies of the rates of microcephaly and other neurological disorders should be conducted in other areas known to have had Zika virus transmission but where such clusters were not observed.
  • Research should continue to explore the possibility of other causative factors or co-factors for the observed clusters of microcephaly and other neurological disorders.
  • To facilitate this research and ensure the most rapid results:
    • surveillance for microcephaly and GBS should be standardized and enhanced, particularly in areas of known Zika virus transmission and areas at risk,
    • work should begin on the development of a potential case definition for ‘congenital Zika infection’,
    • clinical, virologic and epidemiologic data related to the increased rates of microcephaly and/or GBS, and Zika virus transmission, should be rapidly shared with the World Health Organization to facilitate international understanding of the these events, to guide international support for control efforts, and to prioritize further research and product development.

Surveillance

  • Surveillance for and notification of Zika virus infection should be enhanced with the dissemination of standard case definitions and diagnostics to areas of transmission and at-risk areas; newly infected areas should undertake the vector control measures outlined below.

Vector control

  • Vector surveillance, including the determination of mosquito vector species and their sensitivity to insecticides, should be enhanced to strengthen risk assessments and vector control measures.
  • Vector control measures and appropriate personal protective measures should be aggressively promoted and implemented to reduce the risk of exposure to Zika virus.
  • Countries should strengthen vector control measures in the long term and the Director-General of WHO should explore the use of IHR mechanisms, and consider bringing this to a forthcoming World Health Assembly, as means to better engage countries on this issue.

Risk communication

  • Risk communication should be enhanced in countries with Zika virus transmission to address population concerns, enhance community engagement, improve reporting, and ensure application of vector control and personal protective measures.
  • These measures should be based on an appropriate assessment of public perception, knowledge and information; the impact of risk communication measures should be rigorously evaluated to guide their adaptation and improve their impact.
  • Attention should be given to ensuring women of childbearing age and particularly pregnant women have the necessary information and materials to reduce risk of exposure.
  • Information on the risk of sexual transmission, and measures to reduce that risk, should be available to people living in and returning from areas of reported Zika virus transmission.

Clinical care

  • Pregnant women who have been exposed to Zika virus should be counselled and followed for birth outcomes based on the best available information and national practice and policies,
  • In areas of known Zika virus transmission, health services should be prepared for potential increases in neurological syndromes and/or congenital malformations.

Travel measures

  • There should be no general restrictions on travel or trade with countries, areas and/or territories with Zika virus transmission.
  • Pregnant women should be advised not travel to areas of ongoing Zika virus outbreaks; pregnant women whose sexual partners live in or travel to areas with Zika virus outbreaks should ensure safe sexual practices or abstain from sex for the duration of their pregnancy.
  • Travellers to areas with Zika virus outbreaks should be provided with up to date advice on potential risks and appropriate measures to reduce the possibility of exposure to mosquito bites and, upon return, should take appropriate measures, including safe sex, to reduce the risk of onward transmission.
  • The World Health Organization should regularly update its guidance on travel with evolving information on the nature and duration of risks associated with Zika virus infection.
  • Standard WHO recommendations regarding vector control at airports should be implemented in keeping with the IHR (2005). Countries should consider the disinsection of aircraft.

Research & product development

  • The development of new diagnostics for Zika virus infection should be prioritized to facilitate surveillance and control measures, and especially the management of pregnancy.
  • Research, development and evaluation of novel vector control measures should be pursued with particular urgency.
  • Research and development efforts should also be intensified for Zika virus vaccines and therapeutics in the medium term.

Based on this advice the Director-General declared the continuation of the Public Health Emergency of International Concern (PHEIC). The Director-General endorsed the Committee’s advice and issued them as Temporary Recommendations under IHR (2005). The Director-General thanked the Committee Members and Advisors for their advice.

Zika virus: scientists a step closer to establishing microcephaly link

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Although not a concrete link to microcephaly, study shows that Zika can infect cells similar to those involved in brain development and disrupt cell growth

Scientists examining the link between the Zika virus and microcephaly in babies have discovered that the virus can infect cells similar to those involved in brain development.

Published in Stem Cell Stem the study, led by scientists at Johns Hopkins University and Florida State University, reveals that when lab-grown neuronal cells are exposed to the Zika virus, it infects the cells and is able to produce a large number of copies of itself. The researchers also found that the virus was able to disrupt pathways within the cells and limit their growth.

However, the scientists are quick to point out that their results do not prove that the mosquito-borne virus is leading to abnormal brain development of babies in the womb. “We don’t have the direct evidence to show that this will link the Zika virus to microcephaly,” said Dr Zhexing Wen, a co-author of the paper from Johns Hopkins University.

In order to probe the effect of the virus on neuronal cells, the scientists took human skin cells and “reprogrammed” them into pluripotent stem cells, which were then encouraged to grow into cells known as human cortical neural progenitor cells (human NPCs). These cells are similar to those that lead to the development of the cortex – the region of the brain that is typically underdeveloped in babies born with microcephaly.

The cells were then exposed to Zika virus. After 56 hours 65- 90% of the cells were infected with Zika; the virus was also found to be able to reproduce in large numbers within infected cells. What’s more, the Zika virus was found to interfere with cell processes and to increase cell death.

“This study hasn’t directly proved that the Zika virus causes microcephaly,” said Wen. “But it is telling that the human NPCs are very susceptible to the Zika virus and the Zika virus can cause the disruption of the human NPC growth and this may potentially correlate to the disrupted brain development in the foetus.”

While the Zika virus has previously been found to infect a range of human cells types, the latest study reveals that human NPCs showed a greater susceptibility to infection than some other cell types, including human embryonic stem cells. “We also want to know why the human NPCs are quite specific for the infection,” Wen adds.

There are, however, many more questions. “Maybe different strains of the Zika virus have different effects or maybe different people in different areas of the world may have a different response to the same Zika virus,” says Wen. But he believes the technique used by the team could help to provide answers. “We can test this out with the human NPC system,” he says.

Wen adds the team now want to use the human NPC system to screen for drugs that could prevent or eradicate infection by the Zika virus.

Responding to the paper, Prof Jonathan Ball from the University of Nottingham urges caution in interpreting the study’s findings. “There are still a number of unknowns,” he says. “It isn’t clear if the virus growing in the laboratory in these artificially generated nerve cells behaves the same way as it would in a human. We are complex organisms and lots of factors can affect how a virus infection pans out.”

However, he does believe the findings are a step towards probing the impact of Zika on the human body. “These are really interesting findings and go some way to understand how Zika virus might be causing the serious conditions that it is associated with,” he adds. “But we must remember, at the moment Zika and the link to microcephaly and Guillain-Barré [a neurological condition that can cause temporary paralysis] are only associations, and we need to know what is really happening in natural infection. Unfortunately we don’t have all of the tools to be able to do this work and the necessary experiments are tricky to do.”

Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, believes such in vitro research builds on a range of studies exploring the link between the Zika virus and microcephaly. “It’s all accumulating complementary evidence,” he says.

“It is important to understand and definitively prove – or not – the direct causal relationship between infections during pregnancy and microcephaly. As the weeks and months go by there is more and more evidence that is becoming almost compelling that there is a direct causal link,” he told the Guardian.

“I think it is reasonable to make the assumption that sooner or later we will find definitive proof that Zika is related to microcephaly,” he adds. “Then we have a compelling need to protect pregnant women and women of childbearing age who will become pregnant.”

While there is currently no vaccine available to combat the virus, Fauci says that several are under development, with phase one trials for the first vaccine scheduled to begin towards the end of the summer. “Barring any unforeseen glitches I would think we would start that in September,” he says. “By the end of 2016, early 2017 we will know if it is safe in normal people.”

However finding out if it works could take time. “Everything is going to depend on the state of the epidemic because if [it] dies down it might take a couple of years to show that the vaccine works,” says Fauci. “If the epidemic is raging as it is now in early 2017, we may actually know whether it works by the end of 2017.”

10-Month-Old Boy with Microcephaly and Episodic Cyanosis .

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A 10-month-old boy with microcephaly and developmental delay was admitted to the hospital because of episodes of respiratory distress and cyanosis. Microcephaly was present at birth, and hypotonia was noted at 5 months. On admission, brain MRI revealed decreased myelination.

Microcephaly literally means “small head.” It is diagnosed when the head circumference is more than 2 SD below the mean for age and sex, although sometimes a stricter cutoff of 3 SD below the mean is used. The underlying causes of microcephaly can be divided into nongenetic and genetic causes.

Clinical Pearls

• What are some examples of nongenetic and genetic causes of microcephaly?

Common nongenetic causes of microcephaly include intrauterine infections and in utero exposure to drugs, toxins, and ionizing radiation. Other nongenetic causes include disruptive brain injuries and systemic disorders. Genetic causes of microcephaly appear to be diverse; more than 200 genes are associated with microcephaly in the Online Mendelian Inheritance in Man database. MRI of the head can be helpful in guiding genetic testing, because many genetic disorders that occur in patients with microcephaly are associated with characteristic structural abnormalities. Microcephaly is a feature of various syndromes, such as the Rubinstein-Taybi syndrome (which iS characterized by intellectual disability, postnatal growth retardation, broad thumbs and halluces, and dysmorphic facial features) and the Cornelia de Lange syndrome (which is characterized by unique facial features, prenatal and postnatal growth retardation, and intellectual disability and often by upper-limb anomalies).

• What is MTHFR deficiency and how is it diagnosed?

MTHFR is an inborn error of metabolism, in which deficiency of functional methionine synthase traps folates in the 5-methyltetrahydrofolate (5-MTHF) form, consequently causing a deficiency of other active forms of folate (including tetrahydrofolate [THF], 5,10-methenyl-THF, 5,10-methylene-THF, and 10-formyl-THF) and thereby resulting in megaloblastic anemia. In the severe form of MTHFR deficiency, the 5-MTHF level is reduced but anemia is not seen, because the 5,10-methylene-THF and other active forms of THF (including 10-formyl-THF) that are required for purine   and pyrimidine synthesis are not affected. The combination of homocysteinemia, low methionine levels, and absence of anemia indicated a diagnosis of severe MTHFR deficiency.

Morning Report Questions

Q: What are the manifestations of severe MTHFR deficiency?

A: Severe MTHFR deficiency is extremely rare but is the most common disorder of folate metabolism. Approximately 100 cases have been reported, and fewer than 15 have manifested before 6 weeks of age. The clinical presentation is nonspecific, with some age-related variations. In the newborn period and during early infancy, seizures and acute neurologic deterioration are the common initial manifestations, whereas in older infants and children, nonspecific psychomotor deterioration, acquired microcephaly, and abrupt deterioration (e.g., respiratory failure) can be seen. In older patients, isolated stroke, arterial or venous thromboembolic disease, and combined degeneration of the spinal cord have been reported as initial manifestations.

Q: How is MTHFR deficiency treated?

A: Treatment of the remethylation defects is directed toward reducing homocysteine levels (thereby lowering the risk of thromboembolism) and normalizing methionine levels (and normalizing the availabilitY of methionine in the central nervous system). These are achieved through betaine supplementation, which remethylates homocysteine to form methionine through an alternative pathway present in the liver and kidney. Additional treatment involves folate and cofactor supplementation for enzymes in the pathway; hydroxocobalamin (a cofactor for methionine synthase) and riboflavin (a cofactor for MTHFR) are administered to enhance residual activities and improve remethylation, and pyridoxine (a cofactor for cystathionine [beta]-synthase) is administered to enhance degradation of homocysteine through the degradation pathway.

– See more at: http://blogs.nejm.org/now/index.php/10-month-old-boy-with-microcephaly-and-episodic-cyanosis/2014/08/29/#sthash.VPxqrLGc.dpuf