Welcome to Connecting the PWS Dots

Connecting the PWS Dots is an effort to understand the biochemical and other physiological processes underlying Prader-Willi syndrome (PWS) and explore possible interventions for it that began when a friend had a baby with PWS. Given that PWS was identified as a distinct genetic syndrome in 1956, I initially assumed that it had been pretty well characterized in terms of such critical aspects as energy metabolism during the 50 years since then. I was wrong. Instead I found that many aspects of PWS such as cellular energy metabolism have yet to be investigated and are very poorly understood. Hence this effort to weave together research findings, the invaluable expertise of parents of those with PWS, and muscle biopsy and lab tests results in order to better understand PWS so that possible treatments can be identified and trialled.

Many aspects of PWS, including its associated hypotonia, lethargy and hypersomnolence, as well as the positive benefits provided by Coenzyme Q10 for at least some with PWS, strongly suggest impaired energy metabolism, including possible mitochondrial dysfunction. I therefore suggested to my friend that she try carnitine supplementation for her baby because it plays a key role in mitochondrial function and cellular energy production. The results, described in the carnitine article, were dramatic and greatly reinforced the suspicion that impaired energy metabolism plays an important role in the symptomology of PWS.

Since then, work with parents on the HolisticPWS e-mail group and analysis of the muscle biopsies and lab test results that they've generously shared, together with recent landmark research such as the Stefan study (which was funded in part by the Foundation for Prader-Willi Research), have provided the basis for beginning to "connect the PWS dots" and the development of a new picture of PWS - one in which impaired mitochondrial function and energy metabolism play an important part in the hypotonia, lethargy, cognitive impairment, behavioral problems, impaired growth and development, hyperphagia and other symptoms usually considered typical of PWS. Indeed, it is becoming increasingly clear that PWS can be conceptualized at least in part as an inborn error of metabolism.

Currently, there are several articles and other materials here about important issues for parents and other caretakers of those with PWS. In addition to the above-mentioned articles about carnitine and Coenzyme Q10, they include:

• Important information to know about impaired respiratory function in PWS, particularly in infants and children.
• A compilation of the safety guidelines for growth hormone treatment of those with PWS as recommended by PWS clinicians, researchers, growth hormone manufacturers, and the U.S. Food and Drug Administration (FDA).
• Muscle biopsy reports for two infants subsequently diagnosed with PWS (UPD), showing significant impairment in mitochondrial respiratory chain transport complexes I through IV, as well as abnormal muscle morphology (structure) and glycogen and lipid storage abnormalities. Parents of those with PWS are encouraged to print out the biopsy reports together with the Stefan study (which found significantly impaired energy metabolism in a PWS mouse model) and the Wassmer report of mitochondrial deficiency in two children with PWS as background materials for their pediatrician and other health care providers, including a metabolic specialist.
• World Health Organization (WHO) growth charts, which some may find a useful adjunct to the CDC growth charts used in the U.S. Also included is a downloadable spreadsheet for converting from U.S. to metric measurements and calculating BMI according to the formula used by WHO.

In addition, the Research Notes and Research Database contain notes and research journal abstracts about PWS-related topics, and the PWS Dots Journal is where I outline and update the status of various aspects of PWS that I'm investigating. There are other articles in the works regarding various aspects of PWS, so if you have found the information here useful, you might like to subscribe to the Update E-mail List.

Please note that I am not a licensed medical professional, so it is important that you use your good judgment and intimate knowledge of your child, as well as the advice of your health care providers, before acting on the information contained here.

Connecting the PWS Dots is dedicated to little Sullivan and her family, as well as all of those with PWS and their parents, and the new generation of researchers pushing beyond the limits of the current paradigm about PWS.

Thank you for visiting, I hope you find this web site helpful as you face the many challenges posed by PWS. Feedback (whether good, bad or indifferent :-) is always welcome.

Oneida Kincaid
September 2006