Tag Archives: whole genome sequencing

Bringing the Promise of Precision Medicine to Rare Disease

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My latest post as part of my work at Fabric Genomics.

Precision medicine is a form of medicine that uses information about a person’s own genes or proteins to prevent, diagnose, or treat disease.1 When we think of precision medicine, we often focus on cancer and the recent efforts to specifically target treatment based on the genetic composition of a tumor (somatic) or the person’s germline. While it is early days, the health gains of this approach are quite significant with better outcomes shown in multiple studies2 and even data showing lower overall health costs.3 However, the point of precision medicine is not only to optimize treatment for cancer, but also to target health interventions generally for all conditions. In fact, we see the application of precision medicine to high volume diseases such as diabetes and heart disease and even lifestyle interventions such as diet and exercise.

Nowhere is this more challenging than for patients suffering from a rare disease. Ironically it is common to have a rare disease. More than 25 million Americans and more than 400 million people worldwide suffer from one of over 7000 rare conditions, defined as those conditions having an incidence of 1 in 200,000 or less. Precision medicine has focused on big data approaches to studying more common conditions, thereby leaving out those with rare conditions. Lacking a diagnosis, most of these patients and their families are on a “diagnostic odyssey.” These patients typically spend more than five years seeking accurate diagnosis and might see up to eight doctors, often receiving many misdiagnoses and differing opinions on their journey. Along the way, they may be exposed to harmful treatments and invasive testing. It is clear that comprehensive genetic testing gives the best possibility of getting to the exact diagnosis efficiently. Still, historically, genetic data have been available to a minority of patients: only those referred to a clinical geneticist for testing.

For the complete post see https://fabricgenomics.com/2020/12/bringing-the-promise-of-precision-medicine-to-rare-disease/

Improving Health Outcomes for Infants with Pompe Disease

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Fourth post as part of my work at Fabric Genomics

By Martin Reese & Laura Yecies

It was terrific to see this paper by our long time collaborator Arindam Bhattacharjeeon the use of NGS as a second-tier test for Pompe Disease (PD). This is part of an important diagnostic trend of earlier (even to the point of first-line for selected infants) use of NGS as a diagnostic tool that can dramatically improve the newborn’s projected health outcome. Pompe Disease is a perfect example of how this can work.

Background

PD is one of several glycogen storage diseases with variable timing of onset and rates of progressions. According to NORD, “Pompe disease is a rare multisystem disorder caused by pathogenic variations in the GAA gene containing the information for production and function of a protein called acid alpha-glucosidase (GAA). Because of the shortage of this protein (an enzyme), a complex sugar named ‘glycogen’ cannot be degraded to a simple sugar like glucose. This causes the glycogen to accumulate in all kinds of tissues, but primarily in skeletal muscle, smooth muscle, and cardiac muscle, where it causes damage to tissue structure and function. Pompe disease is inherited as an autosomal recessive genetic trait.” Early diagnosis and initiation of treatment are of paramount importance at no later than two weeks of age to minimize muscle damage and avoid significant negative impact on the quality of life.

For the full post please see Fabric’s site here

Accuracy is the New Speed

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Second post as part of my work at Fabric Genomics

By Martin Reese & Laura Yecies

When caring for a critically ill child, two simultaneous thoughts are competing – the urgent need for a diagnosis to optimize treatment and the need for thoroughness – to carefully review all the possibilities.  Don’t jump to a conclusion but don’t get lost in the weeds keeping the patient, and the others behind them, in limbo.  We commonly see accuracy and speed as a dichotomy.  This has certainly been true in the past in genomics – how many variants to review? Review variants from less likely parts of the genome? Use a more restrictive filtering rule?

We had been operating in a world where deciding to use some of the heuristic shortcuts or to time limit review meant settling for less than optimal accuracy. Time-saving techniques left some diagnoses on the cutting room floor.  These simple Pareto prioritizations that are highly effective in dealing with everyday clinical situations are inherently problematic in the rare disease world.  We cannot eliminate the zebras when we know it’s unlikely to be a horse…

Read more on the Fabric website here