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Posts from the ‘Newborn screening’ Category

Newborn Screening for “Bubble Boy Disease”: Interview

On the 1st of January, the state of Wisconsin made a major step in the field of newborn screening. The collaboration of Wisconsin State Laboratory of Hygiene, Children’s Hospital of Wisconsin and the Jeffrey Modell Foundation resulted in screening newborns for Severe Combined Immune Deficiency (SCID). According to the Wikipedia article this is:

…a genetic disorder in which both B and T cells of the adaptive immune system are crippled, due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency. It is also known as the “bubble boy” disease because its victims are extremely vulnerable to infectious diseases.


I’ve already presented The Jeffrey Modell Foundation (headquarters in New York) to you in June. Now, to know more about this medical breakthrough, Dr. Jack Routes from the Children’s Hospital of Wisconsin answered some of my questions:

  • How common is the so-called “Bubble Boy Disease” in the US and in your hospital?

There is no good data on the actual incidence of the disease in the US. It is estimated that at least 1:100,000 newborns have SCID. Our newborn screening program will better ascertain the true incidence of SCID in Wisconsin.

  • Is a blood sample taken from a newborn enough for the screening process?

All newborn screening tests are performed from blood spotted on a newborn screening card—the newborn gets a heel stick and blood is put on a special filter paper on the newborn screening card. A small punch is taken from the filter paper and the SCID screening test is performed.

  • Please tell us some more details of the screening of SCID! How sensitive and predictive is the test?

Please see the article ( J Allergy Clin Immunol. 2005 Feb;115(2):391-8.) for a discussion of the assay. These are the only published data to date. The assay is a real time, quantitative PCR that measures the number of T cell receptor excision circles (TRECs) in the punch from a newborn screening card. TRECs are a surrogate marker for functional, naïve T cells, which will be reduced in most, but not all causes of SCID. Our group has improved the TREC assay (false positive rate is <0.01%) over the results reported in the JACI paper. There is no data on sensitivity and positive predictive value of the test—-this issue will be addressed by the WI SCID screening program.

  • Do you plan to add new medical conditions to the newborn screening program?

Wisconsin constantly evaluates other genetic diseases to add for newborn screening. The WI Newborn Screening Umbrella Committee addresses this issue and I am not a member of this committee and do not know if other tests are being considered in the near future.



I’m thankful to Dr. John Routes for the answers. This is a great example of how to construct a successful newborn screening program. Just to show you the difference, in Hungary, they screen newborns for only 4 (while they screen for 47 in Wisconsin) genetic conditions (galactosaemia, congenital hypothyreosis, biotinidase deficiency and phenylketonuria)

Videojug Beta: Videos about Health and Medicine

After returning from my (successful) pharmacology exam, I have to tell you about a new video-site, Videojug.

VideoJug hosts one of the world’s largest, most all-encompassing libraries of factual content online. Our professionally-produced, high definition video content covers every conceivable topic and delivers the definitive online “encyclopedia of life”. The content is divided into a variety of formats that include informative “How To” and “Ask The Expert” films.

Check out the site for many many health or medicine-related videos, and here are my favourite ones:

Why is it different from other similar sites?

  • You can meet the expert
  • You can easily jump from one chapter to an other
  • You can download the videos
  • The structure of the videos are the same

More medical videosites:

Personalized Genetics/Genomics: Blogterview with Steven Murphy, MD

I’ve recently decided to deepen my knowledge on the field of personalized genetics/genomics as it has an exceptional future in the realm of medicine (and business). And who is the right person to answer my geek questions? Of course, Steven Murphy, MD, the blogger of the Gene Sherpa. He is the Clinical Genetics Fellow at Yale University and is also the founder of a Personalized Medicine practice.

  • We’ve heard a lot about personalized medicine, but please tell us more about personalized genetics.

Sure. There are some fundamental differences here. When I think about personalized genetics (Which is different than personalized genomics) I think about modifier genes involved in single gene disorders such as Cystic Fibrosis. A few months ago, I diagnosed a 70 year old woman with CF. She had been treated as if she had emphysema, had never smoked, and no Alpha 1 Antitrypsin deficiency. Something didn’t sit right with me. We had her get sweat tested and sequenced. Guess what? Compound heterozygote with one Delta 508 mutation. How could this happen? Modifier genes. There is a nice review of modifier genes in CF several months back in the New England Journal of Medicine. That is personalized genetics in my opinion…

Should we treat you aggresively or not? This woman clearly did ok without Creon (pancreatic enzymes), aggressve pulmonary toilet, or inhaled antibiotics. Now with the newborn screen we detect so many more patients with Cystic Fibrosis. Who should we treat? How should we treat? Personalized Genetics is like personalized medicine for those with single gene disorders. I remind you that “No gene is an Island” so we need to take it in context of the rest.

  • Personalized genetics or genomics? Is there any important difference?

Personalized Genomics is a totaly different animal. Here we deal with what everyone affectionately calls the “Personal Genome”. This is the dream of everyone gets a genome sequenced at birth, we assess risk, create prevention plans, identify idosyncratic drug reactions prior to medication therapy. The fear is obvious…”When is GATACA coming?” I think that we need to put protections in place to prevent discrimination from more than just employers and insurers. What about that University you want to get in to? In addition there are several problems with whole genome screening aside from its multimillion dollar pricetag (which is dropping quickly). That is the problem in medicine known as the incidentaloma.

Quite often when ordering a CT scan, or chest xray, or what ever radiologic test we find tumors/cysts/masses in a completely asymptomatic patient. Does this mean we identify a cancer or other life threatening thing before it can cause damage? Sometimes, but more often than not we end up spending thousands of dollars evaluating something that turns out to be nothing. Just an incidental finding in an otherwise asymptomatic patient. An article entitled The incidentalome: a threat to genomic medicine.” was published in JAMA in July of 2006. Mathemeticians modeled sequencing the whole genome. As they get up to sequencing 10.000 people they find that the fraction of the population with a false positive result skyrockets up to 60%. What does this mean? Well, we have to carefully select who we test. Or better yet we need an immense database of “Normal Variants”. At a minimum we will need 1000s of “sequence specialists” or “computer sequence analysis programs” to evaluate and decide if the “work up” is indicated or not. Personal Genomics is very complex, even more than personalized medicine.

  • What about the big companies focusing on personalized genomics/genetics?

We have key players including Illumina, 454 who has now been eaten by Roche, Affymetrix, Ventner, I could go on and on. The newest one to watch for is from the brainchild of 454 Jonathan Rothberg. He is launching a company called RainDance technologies. RainDance is already collaborating with Bayer Pharmaceuticals on high-throughput screening assays, noting the vastly superior statistics and reagent costs. What this means is a whole new means to sequence. If you add that into the nanopore sequencing mix at Harvard, then you have a robust field for development. I am sure I have missed a few, but these seem to be the key and future players to me.

As for personalized genetics, I know that the old stalwards like Genzyme, Genentech, BioMarin are all playing a role in defining the right infusion/pill for the right person with the right monogenic disease. Also you cannot forget about TGen who is building a presonalized medicine medical school in Arizona. My gosh I could just ramble about all of these things, but I will spare you all the details.


  • As bioinformatics plays an important role in this rising field of medicine, how can web (especially web 2.0 ) help personalized genetics?

Web 2.0 and 3.0 can be best harnessed by networks of researchers sharing findings in open source forum. We need to give up the “Prize” for publication. Instead we need to nurture inter-institutional collaboration. In fact I would say we should prize how many universities were involved in every study. The web infrastructure can allow all of these things. In fact imagine coming up with a question in EST and shipping it to Mumbai for analysis during EST night-time. This is already happening in business. True, research takes more than overnight, but what if we were just talking about design. We could literally be working 24/7 to solve problems!

My dream is just that. The spirit of innovation, collaboration, and revolution all moving to solve the greatest code ever devised…DNA

I’m very thankful to Steven Murphy for the kind answers! Follow his blog for the most interesting news and explanations of personalized genetics.

Newborn screening: behind the scenes

newbornscreening_3.jpgRecently, I had a post about a story of a mother of a boy with MCAD (medium chain acyl CoA dehydrogenase defect) from Texas who is also a member of website. Some days before, Erica Ann Lehotzky, a senior studying microbiology, molecular genetics and also working at the Michigan Department of Community Health’s Newborn Screening lab left a comment on my Medscape interview. I asked her to take us behind the scenes to know more about the newborn screening systems, new tests and the future improvements.

  • When and why did you start to work in a newborn screening lab? Tell us a bit more about you!

I started my job in Michigan’s NBS lab nearly a year ago. I feel very fortunate for being offered the student position, as it’s the most rewarding work I’ve ever done. In May I’ll graduate with my bachelor’s degree in microbiology from Michigan State University, and will probably continue to work at the NBS lab over the summer.

  • You may not know that but in Hungary, babies are screened for only four diseases (phenylketonuria, galactosaemia, biotinidase deficiency, congenital hypothyreosis). In the state of Georgia, this number is 28. The reason is only the financial difference? What do you think?

I believe if even one infant has suffered through a condition that could have been prevented through screening, it should be added to the testing list. From a public health perspective, it is much more cost effective to prevent the symptoms of the conditions through early detection rather than paying for treatment when the child is older. Unfortunately, many governments only take the upfront NBS cost into perspective.

  • You test for over 40 diseases? How can it be possible? I mean you test every baby for 40 diseases or some of these are only for specific diagnostic reasons?

Every live birth in Michigan is tested for all of the diseases on our list. Occasionally we’ll get a “high risk baby,” such as if an older sibling of the infant had one of the disorders. In this case we make that baby first priority and try to get it through the process as fast as possible.

If you would like a full list of the diseases we test for, you can find it here in a pdf document.

We run 6 assays every day. Most only check for one or two of the diseases, however one is run using tandem mass spectrometry. The data produced is analysed and helps determine results for metabolic disorders. Most of the amino acid, fatty acid, and organic acid disorders are tested through this method.

  • You mentioned that cystic fibrosis will be added to the list soon. How will you test for CF?

I’ve been told that when we start testing for CF, it will be done at the same time as the assay that tests for Congenital Adrenal Hyperplasia (CAH).

  • You’re doing research in your lab. The subject is Group B Streptococcus. Tell us about it!

In addition to the NBS lab, I work in a research lab at my university. Much of our research there is on E. coli, but right now I’m on our Group B Streptococcus (GBS) project. GBS is the primary cause of sepsis and meningitis in infants, and can also cause disease in elderly patients. Many people (male and female) can be carriers of GBS without it affecting them. We performed a study a few months ago at our student health center to find the prevalence of GBS in female students. I’m now working on antibiotic susceptibility testing of the isolated GBS strains from that study.

Thank you, Erika, for the kind answers. I’m sure about that this short blogterview helped us to understand better the different newborn screening systems. Below take a look at the image representing the number of screened disorders by states:


If you would like to read more on the subject, don’t miss these sites:

Newborn Screening in the US: a mother’s story about how to improve a whole system

Some time ago, in one of my posts I noted that I was looking for a newborn screening specialist. Then I got a letter from a mother of a boy with MCAD (medium chain acyl CoA dehydrogenase defect) from Texas and I had to realize how incredible story she had. Laura Clow who is also a member of website, kindly answered my questions.

  • Please tell us the story of your boy! How was he diagnosed with medium chain acyl CoA dehydrogenase defect?

Brickman was a full-term, seemingly perfect, healthy baby & toddler, hitting every developmental milestone ahead of schedule. When he was 19 months old, he became ill with a stomach virus. He went 18 hours without food because of the illness. He began having seizures and slipped into a coma. The doctors at the E.R. could not determine what was wrong. His lab-work (which took 3 hours to receive) from the hospital revealed that his glucose level was 7 in the blood and 2 in the spinal fluid. When this was discovered, we were in a critical care ambulance in transport to a children’s hospital in Dallas. The paramedic put glucose into his circulation immediately.

He remained in the coma for 15 hours, was in a Pediatric Intensive Care Unit unit for 2 days and stayed in the hospital for 6 more days. Lab tests were sent to Duke University and it was determined that he had MCAD. My husband and I had genetic testing and he has the most common MCAD mutation and I have one that had not been discovered until that time. We then learned that other states in the USA routinely screened for MCAD in the newborn screening panel and that we could have ordered the test for only $25.00 at the time of his birth if we had only known about it. By the grace of God, Brickman did not suffer any long-term consequences from the metabolic crisis.

  • You told me that your family has been very active promoting awareness of supplemental newborn screening. You even went to the state capitol and testified in front of the Health & Human Services Committee. Why did you do that and what are the results?

When I learned that the state lines in which we lived prevented us from knowing about his condition at birth and that we could have paid $25.00 for a supplemental screening test, I was mad, but determined to make a difference for others. I joined two support groups ( and ) and met many families whose children had died or suffered permanent brain damage from undiagnosed metabolic conditions. I did not want another family to have to endure a tragic experience because of lack of proper newborn screening. Educating others about newborn screening became my passion.

I have worked at many trade show booths, baby fairs, spoken to Mom’s groups, midwife groups and doctors to promote awareness of expanded newborn screening. I would stop pregnant women in the grocery store and tell them about it. I also gave supplemental newborn screening kits with a check for $25.00 to many of my friends.

One day, I contacted my State Representative to express concern about lack of proper newborn screening in Texas. About that same time, the March of Dimes was pushing for states to expand newborn screening programs across the USA. We teamed up with the March of Dimes when Texas was considering expansion of their program in April of 2005. We traveled to the State Capitol and testified in front of the Health & Human Services Committee. There were several other affected Texas families there as well. The proposals passed the House and the Senate, but the expanded screening did not actually begin until December 2006. Texas now screens newborns for 27 inherited disorders – 19 more than before.



  • What are your plans for the near future?

Great Question! I wish I knew the answer! I am looking for a job for the fall because my youngest child will start Kindergarten. I was an elementary school teacher before I had children, and I would like to teach again or work in the field of expanded newborn screening.

The Save Babies Through Screening Foundation is a non-profit, volunteer-run foundation which exists to promote awareness and educate others about expanded newborn screening. The website has many links to the 50 USA state newborn screening programs, information about how to obtain a supplemental screening kit, family stories and more. They also have an email list where families can seek support from others and share information.

I’m totally amazed by the work and enthusiasm of Laura Clow. It became true that mothers like her can improve even a whole system.



MedWatch: genes, genetic tests and newborn screening

Yes, my favourite subjects. This time, I’ve collected all the most important announcements and news on these fields. And I must include a video on the Mysteries of the Human Genome…

The new technique enabled them to rapidly analyze more than 200,000 gene interactions. Each yeast colony grows in a tiny spot on an agar plate, and each plate holds around 750 colonies. Software makes it possible to determine the growth rate of each colony and then compare the effect on growth of eliminating one gene at a time with the effect when two genes are simultaneously disabled.

A large proportion of genetically caused deafness in humans may be reversible by compensating for a missing protein, based on discoveries in mice… There are millions of deaf people affected by mutations in this one gene, connexin26. Gene therapy, which has very few successful cases so far, may not be necessary,” explains Dr. Lin… a drug to boost connexin26 may be all that is needed.

Australian researchers have developed a low-cost genetic diagnostic test for Parkinson’s Disease (PD). The new method employs a ‘gene-sequencing chip’ that screens 17 genes in all, including the six known Parkinson’s disease genes plus some other suspects in one simple test. Volunteers are being sought for both the PD GeneChip trial and the Australia-wide PD gene mapping study.

National experts convened last week to review components of the newborn screening (NBS) process and actions needed to maintain vital NBS and genetic services during and after a disaster such as a hurricane or terrorist attack… The aim is to develop disaster response tools that can be adapted locally, regionally and nationally to ensure that infants at any step in the NBS system, ranging from the newborn heel-stick screen through laboratory testing, diagnosis and long-term management, are able to complete screening in a timely way and maintain their access to critical treatments and specialist care providers.

My dream about the prevention of genetic conditions

nutrigenI think, after 2 and a half months of blogging, it’s time to tell you my dream. I’m nearly sure about that this dream wouldn’t come true in my lifetime. I dream about a total screening for genetic conditions and diseases. When you are born, your DNA is screened for well-known variations and gene abnormalities. These variations lead to increased risk for some kind of diseases. Now, I’m not talking about only monogenic disorders, but multifactural ones: heart disease, gout, some types of cancer.

A predictive gene test can determine if you have gene mutations that increase your chances of developing a disease. Why is it so important? Because you might not have any signs or symptoms of the disorder, but if you have a strong family history of a genetic condition, you might be at risk of developing that. And many of these problems could be treated (e.g. diet, physical activity…) in case the therapy is launched in time.

Recently, I’ve found 3 articles writing about developments in the field of genetic screening, I hope you’ll enjoy them:

Many thousands of people choose each year to test their early pregnancies for serious abnormalities of development. This new technology promises to make these tests, faster, more accurate and better targeted than current methods which have been in use for the past 30 years.

Scientists have successfully tested a technique for identifying newly recognized DNA variations that may influence disease risk. Rather than focus on errors and alterations in DNA sequence, the new technique highlights variations in the number of copies of a particular gene. Additional copies of a gene may lead to overproduction of that gene’s protein, and this may affect both easily identifiable traits such as body size or more difficult-to-discern traits such as cancer risk.

University of Leicester research into variations in the human genome which may have links with serious medical conditions, has received a highly-sought after international award…Professor Brookes said: “This is a much-appreciated and timely award. It will help create an important gene-disease database that will consolidate the ever-increasing flow of genetic discoveries in a way that has true global relevance for mankind’s health and well-being.


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