This week’s NY Times has a most powerful and beautiful essay written by Emily Rapp, entitled “Notes From a Dragon Mom”, in which she describes what it is like to parent a child who is destined to die. Rapp’s 18 month old son Ronan has Tay Sachs disease, a progressive and incurable neurologic disorder that will result in his death within a few short years of life.

How do you parent without a net, without a future, knowing that you will lose your child, bit by torturous bit?

Depressing? Sure. But not without wisdom, not without a profound understanding of the human experience or without hard-won lessons, forged through grief and helplessness and deeply committed love about how to be not just a mother or a father but how to be human.

Rapp’s essay is a foray into the true connection between parent and child, and, in a way, a celebration of how that relationship is all the more special because it is devoid of the pressures of perfect parenting for the perfect future.

Ronan has given us a terrible freedom from expectations, a magical world where there are no goals, no prizes to win, no outcomes to monitor, discuss, compare. But the day-to-day is often peaceful, even blissful.

As a mother, I want to thank Rapp for her wisdom as she shows us all how to be better parents, and wish her continued strength and joy as Ronan’s mom.

As a doctor, I’d like to address the section of the essay where Rapp talks about Tay Sachs gene mutation screening.  It’s a short paragraph with just enough information to answer the question the reader probably has, which is – “How did this happen, when we have prenatal testing for Tay Sachs?”. Unfortunately, it is also just enough information to confuse and even frighten women who have had or are considering having prenatal screening for Tay Sachs.

The prenatal test I took for Tay-Sachs was negative; our genetic counselor didn’t think I needed the test, since I’m not Jewish and Tay-Sachs is thought to be a greater risk among Ashkenazi Jews. Being somewhat obsessive about such matters, I had it done anyway, twice.  Both times the results were negative.

Oy. Let’s see what I can do here…

A TAY SACHS SCREENING PRIMER

What is Tay Sachs?

Tay Sachs is a genetic disorder caused a recessive mutation in the gene for hexosaminidase-A, an enzyme that catalyzes the breakdown of fatty acids in the brain. In the presence of defective Hex-A, fatty acids accumulate in the brain, causing permanent damage and progressive neurologic decline and eventually, death.

Babies born with Tay Sachs carry two copies of the defective gene, one from each parent. Parents who are carriers of recessive genes can be detected though prenatal genetic screening. This screening has been concentrated to date in high risk groups, which in the US are primarily Ashkenazi Jews, who have a carrier incidence of 1 in 30.

Who Should be Screened for Tay Sachs?

At this point in time, prenatal Tay Sachs screening is recommended to be offered to individuals from groups with increased mutation carrier incidence  - Ashkenazi Jews, French Canadians, Louisiana Cajuns and Pennsylvania Dutch. Rapp is of Irish descent,  a group with a mutation carrier incidence somewhere between 1/50 and around 1/200.

Of course, a major reason why couples screen for Tay Sachs, and for other genetic disorders, is because they want the option to terminate an affected pregnancy. An indeed, with the advent of prenatal diagnosis, the incidence of Tay Sachs among children born in the Ashkenazi Jewish population has plummeted.

In addition to using screening prenatally, some Jewish communities screen much earlier, and actually maintain online databases of Tay Sachs carrier information, so that couples can log on and screen out one another before embarking on a courtship, in an attempt to reduce marriages between two carriers. In Montreal, voluntary high-school based Tay Sachs screening programs have led to a 90% decline in the incidence of Tay Sachs in high risk communities.

Tay Sachs – Not Just a Jewish Disease 

Rapp has also written an essay on Salon entitled ” Tay Sachs is not a Jewish disease“, in which she argues that the panel of Tay Sachs genes tested should be expanded beyond the most common mutations found in the Ashkenazi Jewish populations.

…we need to consider more carefully who should get tested for what, and why. As it turns out, there are about a hundred mutations of the Tay-Sachs gene. Unfortunately the common, standard prenatal screening only detects the nine most commonly detected mutations – commonly detected among those of Ashkenazi Jewish descent , like my husband.

…Until gaps like this are rectified, until the testing catches up with the facts, and until insurance companies are willing to redefine the “standard” array of tests, more families will suffer this kind of horrific loss and the great potential of prenatal screening will never be achieved.

In Rapp’s case, she and her husband indeed would have qualified for screening, and I am assuming from the fact that she was tested twice that they knew in advance that her husband was a mutation carrier.

Tay Sachs Carrier Screening

There are two ways to determine if a parent is a carrier for a Tay Sachs gene mutation – DNA testing (carrier screening) and Hexosamindase -A activity levels.

DNA Carrier Testing

Among Ashkenazi Jews, DNA carrier testing will detect up to 99% of carriers. In the case of a couple where only one is Ashkenazi, initially carrier screening the Jewish member of the couple is thus a good way to go, since the DNA screening tests perform so much better in that population.  Then, if that individual screens positive, the next step is to screen the non-Jewish member of the couple. And that’s where the DNA test falls short –  in non-Ashkenazi individuals, it detects at most 60% of affected individuals. In Rapp’s case, the gene she carried was a rare one indeed, having” last surfaced in 1997, among people of Moroccan descent”.  Thus, it is not surprising that Rapp, despite being a mutation carrier, would have had a negative carrier test result using the available DNA testing.

There are to date over 100 known mtutations in the Hex-A gene that can lead to Tay Sachs disease, and we just do not as yet, nor are we likely soon, to have commercially available screening test for every mutation known to date. In the case of a non-Jewish individual married to a Jewish carrier, non-DNA screening for Hexosaminidase-A activity provides a better alternative to DNA testing.

Hexosaminidase-A Activity Testing

Individuals who carry Hex-A gene mutations, while phenotypically normal, have lower than normal levels of Hex-A serum activity on a simple blood test. This test actually formed the basis of the first screening for Tay Sachs, before we had DNA testing, which is thought to me more specific.

In some ways, though, DNA testing is too specific – it’s like searching for 1 of 100 needles in a haystack. And when you only know how to find 9 of those 100 needles, maybe you’re better off using a magnet – Hex-A Activity testing. It may not tell you which gene you have, but at least it tells you whose haystack has the needles. At that point, you would proceed to testing the baby.

Some might even use Hex-A testing as first line testing in an Ashkenazi individual, or combine it with DNA testing to get as close to 100% certainty as possible even in that population. And, as populations diversify through intermarrriage, Hex-A activity levels are being suggested as a better screen that DNA testing.

Of course, even hex-A activity testing isn’t perfect . But it’s pretty darned good.

Testing the Baby

Remember, that even if both members of the couple are carriers, there is only a 25% chance that the child will be affected. So if both members of the couple are Tay Sachs carriers, or if one is a carrier and the other uncertain, then testing the baby is done using CVS or amniocentesis to test for Hex-A activity, DNA or both. CVS and Amnio are both invasive tests with a small but real risk for miscarriage. Preimplantation genetic testing is also available for couples undergoing IVF who wish to screen for Tay Sachs.

But even these test are not perfect. Which, in the end, was the whole point of my writing this post. So let me say it again -

NO PRENATAL DIAGNOSTIC TEST IS PERFECT

We can talk about how to make Tay Sachs screening more effective. We can expand the number of genes we test for, and the number of individuals who are offered screening, in order to come closer to realizing, as Rapp puts it “the great potential of prenatal screening.”

But we cannot, and must not, set up the expectation among women and families that the technology exists and is available that will guarantee them a perfect child. We cannot set up the expectation that technology exists to detect every child with Tay Sachs, or any other genetic disorder, prenatally.

Or, as the National Tay-Sachs and Allied Disease Organization so eloquently puts it -

We are all carriers of recessive genetic diseases but standard healthcare practice does not screen everyone for all diseases because the technology does yet exist to accurately and cost effectively screen everyone.

Which, in the end, brings me back to Rapp’s most excellent essay, which teaches us to love our children for who they our for as long as we have them – whether that is three months, three years, or a lifetime.

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For more information on Tay Sachs Screening

• National Institute of Neurological Disorders & Stroke
• National Tay Sachs & Allied Diseases Organization
• American College of Med Genetics Guidelines 
• ACOG Committee Opinion on Screening 
• American College of Genetics

Folic acid supplementation of breads and cereals has led to a decline in the incidence of neural tube defects like spina bifida and anencephaly in the United States and other nations that have implemented similar measures.

But too much folic acid may lead to an increased risk for colon cancer.

So says UK researcher John C Mathers, who summarizes the current evidence for this conundrum in a well-written review article in this month’s Genes and Nutrition, and highlighted in the Chicago Tribune.

Folic Acid and Neural Tube Defects

Folic acid deficiency is a leading cause of spina bifida and other neural tube defects in newborns, and can be prevented by taking folic acid supplementation during pregnancy. The problem is that the vitamin must be repleted early in pregnancy when the neural tube is forming – a time when many women may not even know they are pregnant. While women attempting pregnancy are advised to get enough folate or take an supplement, almost half of pregnancies in the United States are unplanned, and less than a third of pregnant women get adequate folate

So in the late 1990′s the FDA mandated the addition of folate to bread and cereal products in the United Sates. Other countries worldwide have followed suit. The result has been a decline in the incidence of neural tube defects.

Given early data that folate might prevent colon cancers as well, studies were done to assess the use of higher doses for that very reason.

High Dose Folic Acid and Colon Cancer

Randomized trials of high dose folate supplementation were performed in individuals with a history of precancerous polyps of the colon. Not only did the supplementation fail to protect against polyps (in the absence of aspirin, a known protector against polyps), it doubled the risk of recurrent polyps. In addition, there were more prostate cancers among those who took high dose folate.

Epidemiological data from the US and Canada show a blip up in colon cancer cases after the introduction of folate-fortified foods (mostly breads) in these countries, further supporting the idea that high dose folate supplementation may not be such a good idea.

When it comes to vitamins, more is not necessarily better

Along with recent data on the risks of high dose Vitamin E, this folic acid data is yet another warning that when it comes to vitamins, more is not necessarily better, and can actually cause harm. It’s something to remember as we watch Vitamin D come into vogue as the vitamin to end all vitamins.

What should you do?

Stick with the current recommendations for Folic Acid intake, which in pregnancy and in women trying to conceive is 400 ug daily. ( In women at high risk for having a child with a neural tube defect, the recommended daily dose is 1 mg. ) Your maximum daily intake should not exceed 1 mg.

Read the labels of the foods you buy to be certain that you are not exceeding the daily recommended dose. I checked my bread label, and it only has 2% of the RDA for folate per slice, so I’m not concerned. Cereals can be be higher (especially Total), but vary significantly.

If you are already taking a multivitamin with folate in it, you might want to avoid high folate cereals and breads. And vice-versa.

Apparently, more and more women are nursing each other’s babies, a practice called Cross-Nursing.

I think that it’s just not been our social norm,” said Morgan McFarland, who has been breast-feeding her friend Sarah Griffith’s son since he was just 3 months old. “In some cultures, it is, and you would think nothing of, you know, nursing your neighbor’s child if something happened, or nursing your sister’s baby if she has to go to work.”

California teen gives birth in shower, walks to hospital

LONG BEACH, Calif. (AP) — A 17-year-old girl gave birth secretly at home, then walked four blocks to a hospital with the baby still attached by its umbilical cord.

“I was just a little nervous” when the labor began, Xochitl Parra said Friday from St. Mary Medical Center as she cradled her 8-pound, 3-ounce son, Alejandro.

The boy was normal and “eating like a champ,” said Dr. Jose Perez, director of the Neonatal Intensive Care Unit.

The teenager said she was alone and taking a shower around 5:30 a.m. Wednesday to get ready for school. Then the contractions took over.

“I felt his head coming, so I sit down and pushed so he could come out,” she said.

Parra did not call 911 because the home phone was disconnected, and she did not want to wake the neighbors because it was so early. Instead, she wrapped the baby, got dressed and went to the hospital on foot. (More of the story and a photo at Yahoo News)

Lots of folks find it hard to believe a teen could hide a pregnancy for 9 months, but it’s not as unusual as you might think. You can’t do it if you are rail thin, but heavier teens have an advantage in that folks just think they are gaining more weight. The oversize t-shirt look helps, too.

I had one teen patient some 20 years back who managed to hide her pregnancy even as she made time trials for the swim team one week before delivering a full term infant. This young woman was tall and stocky to start, and the coach just thought she was gaining weight. Her pediatrician didn’t even consider the diagnosis of pregnancy when she presented to him in labor – he sent her to the ER as a possible appendicitis.

By the way, she also managed to keep her A average throughout the pregnancy. As I told the shocked and ashamed mom, this was one pretty amazing girl. I don’t think I could have accomplished what she had at age 16 while pregnant, let alone holding that secret for 9 months.

It’s one of those interesting phenomena that most gynecologists have seen in their practice at least once. You do an HSG, and the woman with longstanding infertility becomes pregnant the very next cycle!

HSG – that’s short for hysterosalpingogram, a study in which dye is injected through the uterus into the fallopian tubes to see if they are blocked or open.

Post-HSG pregnancies happened often enough that we all thought thought it must be a real effect of the HSG. We theorized that the flushing of the tubes must be opening up a previously undiagnosed blockage of the tubes. But we secretly wondered whether what we were really doing was flushing out the bad humors.

As it turns out, our experiences were indicative of a real phenomenon, and our secret theory was not so crazy. In the past decade, several randomized studies have confirmed that doing nothing but performing an HSG increases pregnancy odds by as much as two to three times. (Cochrane review here). Studies have also confirmed that tubal flushing decreases the concentration of cytokines and other inflammatory proteins in the fallopian tube, and reduces sperm phagocytosis (ie, bad humors).

Now, some docs are wondering if flushing of the tubes could become more than just an observed phenomenon but a planned part of infertility treatment.

Researchers at the Karolinska Insitute in Stockholm have published a nice little study in which they randomized couples with unexplained infertility to one of two treatment arms – (a) Clomid (a drug that stimulates ovulation) plus intrauterine insemination or (b) the same plus pertubation (flushing) of the fallopian tubes with an anesthetic solution just prior to insemination.

Among the 67 patients whose tubes were flushed, there were 10 clinical pregnancies (15%) vs only 2 (3%) in the 63 women whose tubes were not flushed, a statistically significant difference.

But before you get yourself too worked up about these results, it’s worth noting that a fertility-expert friend of mine says that the pregnancy rate in the control group was unusually low, and suspects that this may make the intervention look better than it really is.

In addition, the authors point out that the overall pregnancy rates using this technique are significantly lower than the 30% pregnancy rate expected with IVF in the same population of patients. But their lower tech method is cheaper and faster, and they propose that it may be appropriate for couples who either don’t want IVF or want to do something while they are waiting for IVF.

It’s an interesting idea that needs a bit more study before implementing it outside a research setting. Stay tuned…
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Disclaimer – I am NOT a fertility expert, just a plain-old gynecologist reading the latest literature and doing a little wondering. My little musings should not be mistaken for medical advice. The best person to decide your teatment is your doctor, not me.