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Learning About Your DNA and Childbearing

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Please consider privacy issues if you're planning to have your DNA analyzed. I recommend organizing a group purchase of kits so that it's hard to know who got which kit and then registering the kits through an anonymous email address. Or you might ask your midwife to serve as an anonymizing intermediary.

MTHFR and your Pregnancy - This is an excellent presentation of the issues

What Is MTHFR...in simple terms! with Dr. Eric Berg DC - Really great video that breaks the MTHFR mutation down into understandable terms.

Folic Acid vs Folate — What's the Difference?


Folic acid is completely man-made whereas folate is a natural nutrient from food primarily greens. Some manufacturers of vitamins for example will label folate and then after the word folate state that it is indeed folic acid. in this instance it is folic acid, not natural folate, and they are using folate as an all-encompassing term.

Foods that are processed such as breads, pasta, cookies just to name a few are going to have folic acid added to them. If you read a label and it says folate only, and there is nowhere in the ingredients list what type of folate it is you can contact the company to verify what they are using in their product. Another way to tell if folic acid is in it is if it says enriched.
Doctors are prescribing folic acid and even EXTRA folic acid as a solution to this mutation.

RULE # 1 of the mutation is NEVER ingest folic acid. NEVER! It is like poison to us. If your doctor prescribed you folic acid knowing that the gene is specifically responsible for breaking down folic acid (as this is basic genetics 101), knowing the mutation creates a deficiency in the ability to convert folic acid to methylfolate, they are an idiot. That is all.

If you have methylation issues or don't know your methylation status, it's particularly important during pregnancy to make sure that you're getting the bioactive forms of supplements.  In addition, it's important to avoid the inactive forms because they can block receptors for many days.  Be warned that many processed foods, including mainstream breads, are supplemented with inactive folic acid, sometimes also called folate.

As a general recommendation for most women, good prenatal vitamins with bioactive forms of B9 (folate) and B12 are available from Thorne (Basic Prenatal). Their Vitamin B6 is provided as pyridoxal 5-phosphate, the bioactive form of B6, instead of the more common Pyridoxine HCl form which sometimes cannot be converted into P-5-P in cases of nutritional inadequacies, certain medications, compromised liver function, and enzyme defects.

I used to recommend the Metagenics (Wellness Essentials® Pregnancy or Fem Prenatal®).  Unfortunately, the Metagenics formulas have inactive Vitamin B6 from pyridoxine HCl, which can contribute to the nausea of pregnancy. (Some people also really like NATURELO Prenatal Whole Food Multivitamin and Best Nest. I have heard that Smarty pants is owned by Merck, and Garden of Life was just bought out by Nestle.)

You can get the biologically active forms of B vitamins from Thorne's Methyl-Guard Plus®:
Riboflavin (as Riboflavin 5'-Phosphate Sodium) 90 mg
Vitamin B6 (as Pyridoxal 5'-Phosphate) 45 mg
Folate (as L-5-Methyltetrahydrofolate from L-5-Methyltetrahydrofolic Acid, Glucosamine Salt) 3 mg
Vitamin B12 (as Methylcobalamin) 3 mg

Biologically Active Forms


Levomefolic acid (INN) (also known as 5-MTHF, L-methylfolate and 5-methyltetrahydrofolate and (6S)-5-methyltetrahydrofolate, and (6S)-5-MTHF) is the primary biologically active form of folic acid
Calcium folinate (also called, Folinic acid or called 5-formyltetrahydrofolate) [The bio-inactive C-6 isomer, [6R]-5-formyl-tetrahydrofolate (5-HCO-H4F), is not found in Nature. An oral dose of 13.5µmol of [6R]-5-HCO-H4F in humans results in the appearance of the naturally occurring [6S]-5-methyl-tetrahydrofolate and relatively large amounts of other bioactive folates in plasma. from Biochemical Journal.]

Riboflavin 5'-Phosphate Sodium (Vitamin B2)

Vitamin B6 (as Pyridoxal 5'-Phosphate)

Vitamin B12 (as Methylcobalamin or Adenosylcobalamin).  Methylcobalamin and adenosylcobalamin have different functions thus providing a total solution when combined for those with B12 deficiency.  They are both natural.. [Information from seekinghealth.com]

Inactive Forms


Folic Acid, possible anything labeled just Folate

Vitamin B6 (as Pyridoxine HCl)

Vitamin B12 (as Cyanocobalamin or Hydroxocobalamin) - Hydroxocobalamin is a natural form of B12 but is not bioactive; it requires methylation so it not a good choice for those who have methylation or neurological dysfunction.  Cyanocobalamin is synthetic and requires methylation to be utilized and eliminated from the body.

Please note that Floradix Iron + Herbs has synthetic B6 and B12. I was shocked that such a revered pregnancy remedy for anemia isn't as natural as I thought. Gaia Herbs PlantForce® Liquid Iron is free from synthetic (non-bioactive) additives.

What is Methylation and Why Should You Care About it by Alan Miller, ND [1/12/18] from the Thorne web site - this is an excellent, short overview of methylation issues.

I absolutely rail at the recent 23AndMe nonsense blog article about how methylation couldn't be a real issue because humans wouldn't have evolved to have so many disease states from one gene.  Newsflash: the disease states come from ingesting the synthetic forms of the vitamins, combined with common genes. Everyone agrees that we did not evolve with synthetic vitamins!

MTHFR, Folic Acid and Folate: Should I Eat It? BY JOE (MSC NUTRITION), DIETITIAN [Last Updated 6th August, 2017]

MTHFR mutations are well-known genetic variations that can impact folate metabolism.

I could not find a reliable source that lists the exact ratios, but many websites suggest these are the top food sources of L-methylfolate (methylated folate):

Romaine (Cos) Lettuce
Sprouted legumes (buckwheat, mung beans, chickpeas, etc)
Broccoli and cauliflower
Asparagus
Kale and spinach
Cabbage
Fermented foods such as miso and kefir
Berries like strawberries and raspberries
Citrus fruits like oranges and grapefruits


The MTHFR Variant—What Is It? - a very good explanation, from Best Nest Wellness, a company that makes prenatal vitamins with bioactive forms of folate and B12. I don't understand why it has the non-bioactive form of B6 when the bioactive form can help reduce nausea.

Methylfolate Vs. Folic Acid: What Your Doctor Hasn’t Told You

Preparing For Pregnancy With MTHFR Mutations [Updated on 8 Jan, 2014]

Excessive Folate, B12 in Pregnancy Dramatically Ups Autism Risk [3/12/16] - Excessive levels of plasma folate and vitamin B12 during pregnancy have been linked to a dramatic increase in autism risk in offspring, new research shows.   . . . Dr Fallin said that the team was not able to determine whether excessive plasma folate and vitamin B12 levels corresponded to a certain level of intake of both supplements during pregnancy.

[ED: This provides a helpful direction for more focused research.  It seems there may be a common cause between high folate levels in pregnant women and autism in their children.  I posit that the common cause is problems with their methylation genes. Women with genetic methylation problems will run higher levels of serum folate and B12 because their bodies can't clear it.  Even though their serum levels are high, they may actually be deficient in the bioactive forms which can get into the cells.  There's an increased likelihood that their children will also have genetic methylation problems, which affects their ability to clear environmental toxins, which could cause neurological damage leading to autism.  Similar research would benefit significantly from looking at the MTHFR genes of study participants and their children.]

Your MTHFR Status: How Much Mercury is Detoxified vs. Stored? - This great graphic does a really good job of explaining how different combinations of MTHFR gene variations affect your body's ability to handle mercury.

How to Test for MTHFR Mutations and What to Do if You Have Them

Dr. Amy Myers offers a link to allow you to order the dnalife SNP testing; this uses a mouth swab instead of saliva, so you can use it with your newborn.

Folic acid handling by the human gut: implications for food fortification and supplementation. [free full text]
Patanwala I1, King MJ1, Barrett DA1, Rose J1, Jackson R1, Hudson M1, Philo M1, Dainty JR1, Wright AJ1, Finglas PM1, Jones DE1.
Am J Clin Nutr. 2014 Aug;100(2):593-9. doi: 10.3945/ajcn.113.080507. Epub 2014 Jun 18.

Conclusions: The human gut appears to have a very efficient capacity to convert reduced dietary folates to 5-MTHF but limited ability to reduce folic acid.

I haven't been able to verify this, but I read that stork bites are also likely signs of midline defects related to MTHFR.

Maximized Genetics performs a number of DNA tests from a cheek swab, which can be done on a breastfeeding newborn.

23andMe Offers New Genetic Report on Type 2 Diabetes [3/10/19] - The genes for gestational diabetes and Type II diabetes are related, although this is not totally specific to gestational diabetes.

The Plight of Thyroid Patients - People with MTHFR mutations may not be able to metabolize Synthroid and generics properly. This is an excellent explanation of the issues.

IS FOLIC ACID IN YOUR PRENATAL MAKING YOU & BABY SICK? [10/8/19] By Jacqueline

Methylated Prenatal Vitamins


I generally like supplements from Thorne and Metagenics. They're the high-quality supplements recommended by chiropractors and naturopaths.  I particularly like that they are not part of any multi-level marketing scheme.  However, it seems that many fine supplements providers still have some prenatal vitamins that have non-bioactive components.  These can be problematic for the 40% or so of women who have methylation issues, as discussed in the rest of this web page.

For example, some people say that if you take whole foods supplements, then you can be sure you're getting the natural form of folate.  But New Chapter lists their folate in Perfect Prenatal™ Multivitamin as "Folate (as folic acid from culture media)"; this sounds like it might not be bioactive.

There's a new set of high-end prenatal vitamins with bioactive forms of folate, B6 and B12 available from Best Nest Wellness.  As I write this, the following products have only methylated forms of B6, B9/folate, and B12: Mama Bird™ Prenatal Multi+, Mama Bird™ AM/PM Prenatal Multi+, Mama Bird™ AM/PM Prenatal Multi+ Iodine & Iron Free

Be sure to click on "Supplement Facts" for any item you're considering purchasing.  You want to see L-5-Methyltetrahydrofolate (folate), Methylcobalamin (B12) and Pyridoxal-t-Phosphate (B6).

 Getting Your DNA Tested


Please note that as of May, 2018, 23andMe says that it doesn't provide MTHFR analysis, but they do seem to be providing the raw data needed to assess your methylation genes.

Conditions NOT Included In 23andMe - "23andMe does not offer diagnostic testing." They explicitly say that their current 23andMe reports do not include "MTHFR analysis, such as a targeted mutation analysis, methylation analysis or detox profile".

I believe this has always been true of 23andMe. And I know they've had issues with the FDA about medical interpretation. I just wish they would be more explicit about exactly which parts of which genes they report on.

I am troubled by the ways in which 23andMe is distancing itself from the value of information about MTHFR genes. Is there a better all-purpose DNA analyzer that seems to be more supportive of learning one's MTHFR status?

I believe that knowledge is power and that our intelligence allows us to use knowledge to save ourselves untold miseries.  For example, some people have an unfortunate gene that causes myopathy (including unreversible muscle degeneration); simply knowing this allows you to avoid statins or modify your use.  Most pregnant women already have their DNA tested to see if they carry the gene for cystic fibrosis, and couples in certain demographics may have their DNA tested to assess their risks of creating a child with a severe, life-threatening condition.  Reproductive technologies can help couples to make sure they pass on a good gene to their baby.

In addition to some of the major mutations, there are also less obvious mutations that affect the way your body processes your prenatal vitamins.  For about 10% of women, their prenatal vitamins may actually INCREASE their risk of having a baby with tongue tie or other midline defects.  This is how the issue of DNA testing and the MTHFR gene came to the attention of midwives; a baby with a tongue tie cannot nurse well, causing untold miseries for the mother and baby; surgical correction may be an option, but it can be expensive, very difficult, and may not work well.

Most women who have reached childbearing age will not have any major surprises if they get a full DNA analysis.  Still, some women I talk to "don't want to know".

So, it's important for you to know that you can just have your MTHFR gene tested, or you can have your full DNA analyzed but only get a methylation report, including your MTHFR gene status.


23AndMe offers a provider program, which includes a complimentary kit for the provider, herself.  23AndMe provides raw data that can be interpreted at other sites:

Genetic Genie - Methylation and detox analysis from 23andMe results

MTHFR Support offers a Pregnancy Forum and Find A Practitioner feature.


I really like the comprehensive methylation report from Genetic Genie, and I also really enjoyed the tons of information I got from Promethease.com offering medical interpretation of the results from 23AndMe.  I also like their extensive list of prenatal screens for genetic diseases.  But they've recently raised their price to around $200.  (You can get a discount for group purchases.)  There is a less expensive alternative that just looks at a couple of pairs in the MTHFR gene: 677 and 1298; this is available from SpectraCell Laboratories; I've heard the cost is $40.

StrateGene is a genetic analysis program that uses the raw data from 23andMe.  One of my midwife friends liked it in combination with everything else.
1. Focuses on SNPs that have potential clinical implications
2. Provides the biochemical pathways for each gene - not just the isolated SNP
3. Identifies factors which influence SNPs, kinetic impact, and potential associated symptoms and conditions
4. Includes a full bibliography with supporting research

MTHFR from pointofreturn.com - This is a nice explanation of MTHFR issues, and they list four different places that will give methylation reports from the 23AndMe raw data.

As of May, 2021, Sequencing is a new provider of DNA testing. They claim to provide more comprehensive testing than any other provider. I don't have any experience with them.

Carrier Screening for Rare Diseases & Syndromes | DNA Tests - they screen for a very large number of rare diseases.

Their web pages also list many other providers of DNA tests.

MTHFR and Fertility


Tips for TTC with MTHFR

MTHFR and Tongue Tie


See also: Tongue Tie and Lip Tie

MTHFR Gene Mutations: A Beginner’s Guide

Find a Doctor who can help with  MTHFR issues.  Increasingly, midwives seem to be more aware of the MTHFR issue because of the association with tongue tie and breastfeeding issues.  So you might be able to find a midwife locally who can help guide you through testing and adjusting your diet and supplements.  The editor of these web pages is available for phone consulting to provide you with relevant information - contact Ronnie Falcao, LM MS CPM.


The MTHFR Gene Mutation And How To Rewire Your Genetics - The Bulletproof Executive has an excellent explanation of MTHFR issues.

Preparing For Pregnancy With MTHFR Mutations from mthfrliving.com

Folic Acid and Folate Facts and Fallacies - synthetic folic acid isn't absorbed well.  The natural form is folate or L-5 methyltetrahydrofolate.

TONGUE TIE - IS FOLIC ACID TO BLAME? - This is a simple explanation of how synthetic folic acid may be related to tongue tie.

The little known (but crucial) difference between folate and folic acid [3/9/12] from Chris Kresser's blog

The form of folate that can enter the main folate metabolic cycle is tetrahydrofolate (THF). (2) Unlike natural folates, which are metabolized to THF in the mucosa of the small intestine, folic acid undergoes initial reduction and methylation in the liver, where conversion to the THF form requires dihydrofolate reductase. The low activity of this enzyme in the human liver, combined with a high intake of folic acid, may result in unnatural levels of unmetabolized folic acid entering the systemic circulation.

In his lectures, Dr Neil Rawlins implies that for some people with methylation problems, even natural folate may not be assimilable.  He says that berries are the only natural foods that contain the form that can be assimilated by those with the worst methylation problems.

When people have the MTHFR gene mutation, they do not turn folic acid into folate. In addition, the folic acid plugs the receptor sites in cells with an unusable form for these people. With the unusable folic acid in the receptor cites, the body is prevented from being able to use the folate that they do consume through natural food.

Folate vs Folic Acid, MTHFR, and Why I Regret Taking My Prenatal Vitamin - Here's another version of Cara's web page on folic acid; it's a very accessible discussion of why synthetic folic acid causes problems for some women.

Methylation Resources


Dr Neil Rawlins - MTHFR - Sept 2011 - One-hour YouTube video about the methylation genes and recommended supplements.  Great Start Video!

About the MTHFR gene from the NIH's Genetics Home Reference


Folic Acid and Folate Facts and Fallacies - synthetic folic acid is thought to cause cancer and may contribute to asthma in children.  The natural form is folate or L-5 methyltetrahydrofolate.

And, most importantly, an estimated 33 % of people are genetically deficient in the enzyme that converts synthetic folic acid form for it to be used by your body.

So, pregnant mamas, make sure you're getting natural folate, either through better supplements or through superior nutrition.

Any synthetic folic acid in your diet or supplements actually blocks the absorption of natural folate, thus compounding the problem.  Synthetic folic acid is common in prenatal vitamins, many multivitamins and processed foods.

Dr Ghaheri believes that ties form at around gestation week 12-13, not super early as once thought. So it might not be too late to prevent a tongue tie in your baby.

MTHFR and Hyperemesis


People with a double defective MTHFR C677T gene combination will not be able to metabolize the usual (inactive) form of vitamin B6, which is pyridoxine HCl.  This also means that pharmaceutical combinations such as Diclegis and Dilectin also will not be helpful.  They could theoretically make the hyperemesis worse by blocking receptors for the active form.

The active form of vitamin B 6 is pyridoxal 5'-phosphate, which is contained in Thorne's Methyl-Guard Plus.

Anyone with hyperemesis would do well to get their genes tested to see if this is an issue for you, or just switch to Thorne's Methyl-Guard Plus and stop taking inactive forms of the B vitamins.

Treatment for Hyperemesis Caused by MTHFR/Methylation Issues

1) Stop intake of all forms of non-bioactive supplements or supplemented foods.  Many processed foods such as bread and cereal are supplemented with non-bioactive folic acid, or they may even call it folate.  At the top of this web page, there are lists of terms used for bioactive or non-bioactive forms of the supplements.

2) Stop intake of all prenatal vitamins or other supplements and nausea medications which contain non-bioactive vitamins; this includes Diclegis and Dilectin.

3) Supplement with bioactive forms of B6, which is pyridoxal 5'-phosphate; make sure it's from a very reputable supplements source.  I like Methyl-Guard Plus or Pyridoxal 5'-Phosphate 180's from Thorne. The amount of B6 in Diclegis is 10 mg, so this seems like a good goal.  B vitamins are excreted fairly rapidly, so it is unlikely that you would be able to take in excessive amounts.
If the nausea is so bad that you're having trouble keeping the capsules down, you could try opening a capsule (or half capsule, depending on taste) into an ice cube compartment and then freezing it.  Most moms will be able to suck on the frozen ice cube.  And you can absorb the dissolved vitamins through the mucous membranes of your mouth, so you don't even have to swallow it!

4) KEEP YOUR BOWELS MOVING - This is a problem with any case of hyperemesis. You can't keep food down, so your bowel activity slows, so you're not excreting the high levels of pregnancy hormones as quickly as you should be.  You may actually be re-absorbing hormones from your gut to cause higher levels of the hormones which cause hyperemesis. The best remedy is probably maltitol, a pregnancy-safe natural sweetener which has laxative effects. Again, you can sweeten ice cubes with it.  Start out slowly . . . maybe one teaspoon maltitol every six hours or so and increase as needed to achieve the desired result.

It can take up to two weeks for your body to clear out the non-bioactive form of B6, so don't expect a full recovery immediately.  But you should start to see some mild improvement within a few days and some significant improvement within a week.

GDF15 and IGFBP and Hyperemesis


Two genes likely play key role in extreme nausea and vomiting during pregnancy | YouTube video from UCLA Health News [3/21/18]

A new study led by researchers at UCLA and published in the journal Nature Communications has identified two genes associated with hyperemesis gravidarum, whose cause has not been determined in previous studies. The genes, known as GDF15 and IGFBP7, are both involved in the development of the placenta and play important roles in early pregnancy and appetite regulation.

These genes are expressed at high levels in the placenta. They've shown that the associated proteins are abnormally high in women with HG.
They say there's no evidence that HCG and elevated estrogen are related to HG, which seems to contradict long-established teachings.

No relevant therapies are found yet.

Two genes likely play key role in extreme nausea and vomiting during pregnancy - UCLA-led study will help scientists better understand debilitating condition [3/21/18] - research by Marlena Schoenberg Fejzo, the study’s first author, said. She is an associate researcher at the David Geffen School of Medicine at UCLA.


Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum. [Full text from Nature Communications]
Fejzo MS1,2, Sazonova OV3, Sathirapongsasuti JF3, Hallgrímsdóttir IB3,4, Vacic V3, MacGibbon KW5, Schoenberg FP6, Mancuso N7, Slamon DJ8, Mullin PM9; 23andMe Research Team.
Nat Commun. 2018 Mar 21;9(1):1178. doi: 10.1038/s41467-018-03258-0.

Abstract: Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3-2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for comprehending the disease etiology. Here, we conduct a genome-wide association study (GWAS) for binary (HG) and ordinal (severity of nausea and vomiting) phenotypes of pregnancy complications. Two loci, chr19p13.11 and chr4q12, are genome-wide significant (p < 5 × 10-8) in both association scans and are replicated in an independent cohort. The genes implicated at these two loci are GDF15 and IGFBP7 respectively, both known to be involved in placentation, appetite, and cachexia. While proving the casual roles of GDF15 and IGFBP7 in nausea and vomiting of pregnancy requires further study, this GWAS provides insights into the genetic risk factors contributing to the disease.

MTHFR and Vaccination Reactions


Genetic basis for adverse events after smallpox vaccination. [full text]
Reif DM1, McKinney BA, Motsinger AA, Chanock SJ, Edwards KM, Rock MT, Moore JH, Crowe JE.
J Infect Dis. 2008 Jul 1;198(1):16-22. doi: 10.1086/588670.

Identifying genetic factors associated with the development of adverse events might allow screening before vaccinia virus administration. Two independent clinical trials of the smallpox vaccine (Aventis Pasteur) were conducted in healthy, vaccinia virus-naive adult volunteers. Volunteers were assessed repeatedly for local and systemic adverse events (AEs) associated with the receipt of vaccine and underwent genotyping for 1,442 singlenucleotide polymorphisms (SNPs). In the first study, 36 SNPs in 26 genes were associated with systemic AEs (P <or= .05); these 26 genes were tested in the second study. In the final analysis, 3 SNPs were consistently associated with AEs in both studies. The presence of a nonsynonymous SNP in the methylenetetrahydrofolate reductase (MTHFR)gene was associated with the risk ofAEin both trials (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.1-5.2] [P = .04] and OR, 4.1 [95% CI, 1.4 -11.4] [P<.01]). Two SNPs in the interferon regulatory factor-1 (IRF1) gene were associated with the risk of AE in both sample sets (OR, 3.2 [95% CI, 1.1-9.8] [P = .03] andOR, 3.0 [95% CI, 1.1- 8.3] [P = .03]). Genetic polymorphisms in genes expressing an enzyme previously associated with adverse reactions to a variety of pharmacologic agents (MTHFR) and an immunological transcription factor (IRF1) were associated with AEs after smallpox vaccination in 2 independent study samples.

MTHFR and Newborn Screening


In the California Newborn Screening's list of Disorders Detectable by NBS Program as of January 1, 2012, they include  remethylation defects (MTHFR, MTR, MTRR, Cbl D v1, Cbl G deficiencies) .

The Newborn Screen is not a genetic test of the MTHFR gene.  Instead, it measures chemicals in the baby's blood that would indicate very severe problems with remethylation.  The rate of babies identified by this specific tests is only 0.27%, whereas the genetic average for people with homozygous defects is closer to 10%.

Newborn screening for homocystinurias and methylation disorders: systematic review and proposed guidelines. [full text]
Huemer M1,2,3, Kožich V4, Rinaldo P5, Baumgartner MR6,7, Merinero B8, Pasquini E9, Ribes A10, Blom HJ11.
J Inherit Metab Dis. 2015 Nov;38(6):1007-19. doi: 10.1007/s10545-015-9830-z. Epub 2015 Mar 12.

Newborn screening (NBS) is justified if early intervention is effective in a disorder generally not detected early in life on a clinical basis, and if sensitive and specific biochemical markers exist. Experience with NBS for homocystinurias and methylation disorders is limited. However, there is robust evidence for the success of early treatment with diet, betaine and/or pyridoxine for CBS deficiency and good evidence for the success of early betaine treatment in severe MTHFR deficiency. These conditions can be screened in dried blood spots by determining methionine (Met), methionine-to-phenylanine (Met/Phe) ratio, and total homocysteine (tHcy) as a second tier marker. Therefore, we recommend NBS for cystathionine beta-synthase and severe MTHFR deficiency. Weaker evidence is available for the disorders of intracellular cobalamin metabolism. Early treatment is clearly of advantage for patients with the late-onset cblC defect. In the early-onset type, survival and non-neurological symptoms improve but the effect on neurocognitive development is uncertain. The cblC defect can be screened by measuring propionylcarnitine, propionylcarnitine-to-acetylcarnitine ratio combined with the second tier markers methylmalonic acid and tHcy. For the cblE and cblG defects, evidence for the benefit of early treatment is weaker; and data on performance of Met, Met/Phe and tHcy even more limited. Individuals homozygous or compound heterozygous for MAT1A mutations may benefit from detection by NBS using Met, which on the other hand also detects asymptomatic heterozygotes. Clinical and laboratory data is insufficient to develop any recommendation on NBS for the cblD, cblF, cblJ defects, glycineN-methyltransferase-, S-adenosylhomocysteinehydrolase- and adenosine kinase deficiency.

Two-tier approach to the newborn screening of methylenetetrahydrofolate reductase deficiency and other remethylation disorders with tandem mass spectrometry. [full text]
Tortorelli S1, Turgeon CT, Lim JS, Baumgart S, Day-Salvatore DL, Abdenur J, Bernstein JA, Lorey F, Lichter-Konecki U, Oglesbee D, Raymond K, Matern D, Schimmenti L, Rinaldo P, Gavrilov DK.
J Pediatr. 2010 Aug;157(2):271-5. doi: 10.1016/j.jpeds.2010.02.027. Epub 2010 Apr 14.

RESULTS: A total of 86 333 NBS samples were tested between January 2007 and March 2008, and 233 of them (0.27%) met the criteria for second-tier testing of tHcy.


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