Introducing Sylvia Stöckler Ipsiroglu - a Champion of Newborn Screening

bridges vol. 21, April 2009 / News from the Network: Austrian Researchers Abroad

By Karoline Peter

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Dr. Sylvia Stockler Ipsiroglu

One look at Sylvia Stöckler Ipsiroglu's curriculum vitae makes a stunning impression. Her 25-year career as a researcher,pediatrician, and health care manager is impressive enough when examined at each stage, but even more impressive when all of her accomplishments are combined:  Stöckler launched her research career by discovering a metabolic disorder that later became part of newborn screenings in Austria; she then extended and overhauled the screening with new technology as a health care manager during her time in the Department of Pediatrics at the University Hospital in Vienna, and as head of the Austrian newborn screening program. In 2005, she followed a call to head the Division of Biochemical Diseases and the Cystic Fibrosis clinical service at British Columbia's Children's Hospital in Vancouver, Canada. She continues to apply her knowledge and expertise to expand newborn screening in Canada - while still finding time to sit at the bedsides of her young patients.

From a pediatrician to a health care manager

After finishing her Ph.D. at the Karl Franzens University in Graz in 1983, Stöckler completed her residencies and some fellowships before moving to Göttingen, Germany, in 1992 to work in neurology at the August University.

During her fellowship training in Göttingen, her career was serendipitously pushed in a certain direction: In 1994, she was the first scientist to describe the cerebral creatine deficiency syndrome. Her discovery was about a metabolic disorder, more precisely, about a defective enzyme, guanidinoacetate methyltransferase (GAMT), one of the enzymes responsible for creatine production. If not treated, this rare disorder leads to mental retardation, speech delay, and epilepsy. However, if diagnosed early in newborns, treatment is simple by supplementing the patients with creatine monohydrate and ornithine and putting them on dietary arginine restriction. This can be done immediately after birth, reducing brain damage enormously.

After this groundbreaking discovery, her professor suggested extending her stay at August University in Göttingen to continue research in this field. Stöckler did so, and also completed her Habilitation in 1996 while at Göttingen.

Through metabolism, the human body transforms food into energy. Many enzymes are necessary to break down digested food into substances to be used by body cells and turned into energy. Some enzymes are responsible for building up essential compounds that cannot be obtained from nutrition, and others break down components that are no longer needed, which the body wants to get rid of. A genetic defect can lead to enzyme dysfunction (from too little to no enzyme production), which corresponds to mild or severe presentation of a metabolic disease.  

Even today, Stöckler continues to enjoy an international reputation for her 1994 pioneering discovery of the creatine deficiency syndrome. "People still call me up to ask for my opinion on how patients should be treated," says Stöckler. Today, the number of patients identified with creatine deficiency is estimated to be approximately 250. "There might be so many more out there. A few years ago, a child's diagnosis was simply epilepsy and severe developmental delay, but today - especially thanks to the availability of  advanced analytical methods (such as tandem mass spectrometry) - we can diagnose a creatine deficiency disorders early on, and treatment can be started before major damage occurs. Creatine deficiency is also a good candidate for newborn screening," so Stöckler.

In 1996, Stöckler returned to Austria, where she became an attending physician in the Department of General Pediatrics and head of the Unit for Biochemical Diseases at the University Hospital of Vienna. Only one year later, she was appointed to head the newborn screening program in Austria.

{access view=guest}Access to the full article is free, but requires you to register. Registration is simple and quick – all we need is your name and a valid e-mail address. We appreciate your interest in bridges.{/access} {access view=!guest} The history of newborn screening in a nutshell

The US government wants newborns in all states to be screened for 29 medical conditions.

Newborn screening involves quick and simple testing that is implemented to detect dysfunctions at the earliest possible stage. If diagnosed early, a broad range of medical problems or even death can be avoided or prevented by appropriate treatment. It is estimated that, thanks to newborn screening, about 30,000 babies worldwide have been spared from mental retardation, other cognitive disorders, and death.

Newborn screening has more than a 40-year history that started in the Buffalo, New York, lab of Dr. Robert Guthrie, a microbiologist and pediatrician at the State University of New York. A genetic disorder called "phenylketonuria" or PKU, discovered in 1934 by the Norwegian physician Dr. Ivar Følling, was once the leading cause of mental retardation. Before newborn screening became available, PKU was typically not diagnosed before an infant was six months old when developmental delays became apparent. This delay in treatment resulted in severe, irreversible neurological damage. In the 1950s, Horst Bickel, a German doctor, found that treatment based on a phenylalanine-restricted diet could prevent damage and the treated patient could live a relatively normal life - although, once incurred, neurological damage can not be reversed. But the simple, inexpensive test devised by Robert Guthrie allowed pre-symptomatic detection of PKU by measuring phenylalanine in dried blood samples from babies immediately after birth, and made Bickel's discovery applicable for patient treatment.

Once the Guthrie test was introduced in 1961, it rapidly spread around the world. Only two years after the introduction of the Guthrie Test in the US, Austria was one of the first countries in Europe to implement nationwide newborn screening in 1966. From the start, newborn screening in Austria was centralized in the Department of Pediatrics and Adolescent Medicine at the Medical University of Vienna and the program is still federally funded; therefore no costs arise for either the parents or the hospital. Today, Austrian newborn screening includes over 30 disorders. Since not only the screening but also therapy and treatment for all newborns are centrally organized, Austria contributes valuable knowledge from follow-up evaluations about the long-range prognosis for metabolic disorders.

The Introduction of Tandem Mass Spectrometry

In the early 1990s the advent of TMS helped improve newborn screening tremendously:  With one single drop of blood, TMS can screen for up to 40 conditions at once.

Tandem mass-spectrometry, a form of mass-spectrometry, is a multi-analyte analysis technique for the elucidation of the elemental composition of a sample.

Dr. Adelbert Roscher, head of the Department of Metabolism and Molecular Biology at the Dr. von Haunersches Kinderspital in Munich, Germany, was one of the first in Europe to introduce tandem-mass-spectrometry in newborn screening. Stöckler considers him one of the most influential mentors in her career. Following in his tracks, Stöckler expanded newborn screening in Austria in April 2002 by introducing TMS, and thereby nearly quadrupled the number of tested disorders in newborn screening from 6 to 23, including the GAMT-defect. Stöckler had also begun a MAS-Program in hospital management at the University of Economics & Business Administration in Vienna in 2000, and delved into a national database project to investigate the tension between preventive medicine and university-based scientific commitment related to newborn screening.

The state of newborn screening on the other side of the Atlantic: US and Canada

Until very recently, newborn screenings in the US and Canada were at the discretion of each state or province. Organizations of parents whose children had died or suffered because they were born in the "wrong" state have pushed for uniform screening standards.

Only six years ago, in 2003, all but four of the US states were screening for only six or fewer disorders. In May 2005, a federal advisory committee, the Committee on Heritable Disorders and Genetic Diseases in Newborns and Children, set up by the US Department of Health and Human Services (HHS), recommended that all states screen for the same conditions. Finally, in December 2008, the situation referred to by patient advocates and families as "Newborn roulette" was ended in the US. Now there is mandatory screening in all 50 US states and the District of Columbia for 21 or more of the 29 serious genetic or functional disorders, as recommended by the American College of Medical Genetics (ACMG).

When Stöckler came to head the Division of Biochemical Diseases and Cystic Fibrosis clinical service at the British Columbia Children's Hospital in 2005, the numbers of disorders screened for were comparatively low: at that time British Columbia had already introduced the new tandem mass spectrometry based technology, but the total number of diseases screened for was still low; provinces such as Ontario or New Brunswick screened for just three disorders - including hearing (see table below).  However, Canada has recently caught up with the international trend: screening for more than 10 diseases has been introduced in British Columbia and the same happened in all the other provinces.

Newborn screening in Canada - July 2005
Source: Eggerston L. "Pediatric Screening: Canada lags on newborn screening." JAMC Vol. 173, no. 1 (2005): 23.
Province  PKU CH G CAH BD T H No. of other disorders tested
British Columbia  x  x  x        
Alberta  x  x          
Saskatchewan  x  x          
Manitoba  x  x  x  x  x    
Ontario  x  x          
Quebec  x  x        x  
Nova Scotia  x  x          
New Brunswick  x          
Prince Edward Island  x  x          
Newfoundland and Labrador
 x  x        
= phenylketonuria, CH = congenital hypothyroidism, G = galactosemia, CAH = congenital adrenal hyperplasia, BD = biotinidase deficiency, T = tyrosinemia, H = homocystinuria

At British Columbia's Children's Hospital in Vancouver, Stöckler is part of the committee that deals with newborn screening. Asked about her experiences working on such projects in Austria compared to Canada, she says: "A big difference compared to Austria is that here [in Canada] you build committees existing of an interdisciplinary team of clinicians, physicians, dieticians, nurses, and social workers. Everybody is taking over responsibilities and the combined knowledge is extremely contributory to the well-being of the patient."

As head of the Division of Biochemical Diseases, Stöckler also deals with administrative tasks, for example applying for grants. Reading

Stoeckler (left) sitting with her patients.

relevant literature to stay up to date on new developments in newborn screening is also a major and important part of her work. Last but not least, sharing her experience and knowledge with the younger generation of medical doctors is something Stöckler enjoys a lot. "I teach postdoctoral fellows, which means we see our patients together in the clinic or on the wards and discuss their medical conditions to find individually tailored solutions."

Although her leisure time is limited, Stöckler seems to be very balanced: "I am very close to the bedside of the patients. Once you realize a problem, you go to the research lab and try to find out the cause and, subsequently, the treatment for this problem. This combination of both, contact with the patient and research, is what gives me the energy ..."


The author, Karoline Peter, is a nutritional scientist who has done internships in different areas of the life sciences.

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