Rare Disease Education: PGAP3-Congenital Disorder of Glycosylation

Rare Disease Education:  PGAP3-Congenital Disorder of Glycosylation

Editor: Kelsey LaFayette, DNP, RN, FNP-C

"When you hear hoofbeats, think of horses, not zebras,” is a common saying in medical education that means you should think of common conditions first, instead of rare ones, in making a diagnosis. “Rare” is a relative term though and about 7,000 rare, or "zebra," conditions affect more than 350 million individuals worldwide. Although these conditions collectively affect an enormous number of people,  each of these conditions individually is rare enough that it can be difficult to secure the resources to study them and to develop treatments and cures. Likewise, awareness of rare conditions may be low and health care professionals may not be familiar with their signs and symptoms making it more difficult to reach a correct diagnosis and provide effective treatments.  

To increase knowledge about rare conditions, Osmosis and the National Organization for Rare Diseases (NORD) have collaborated on an initiative to bring education and awareness to the public. We are excited to be a part of this initiative because we believe everyone deserves quality health care, no matter how rare their condition.

Zebra of the Week: PGAP3-Congenital Disorder of Glycosylation

The body has countless systems complementing each other and working in harmony. In an orchestra playing a symphony, one musician playing off-key affects the whole resulting music. Similarly, glycosylation is a complex chemical process whereby sugar “trees” called glycans are created, altered, and attached to thousands of proteins or fats serving innumerable functions. In PGAP3-congenital disorder of glycosylation, one gene malfunction affecting the glycosylation process has wide-reaching consequences.

PGAP3-congenital disorder of glycosylation is a rare genetic, metabolic disorder that may manifest as distinctive facial features, intellectual disability, autistic behavior, sleep disturbances, muscle tone issues, and recurrent seizures. It is autosomal recessive, meaning two faulty genes need to be inherited, one from each parent. The first reported case of PGAP3-congenital disorder of glycosylation was in 2012 and there are now upwards of 30 patients with published cases in the medical literature.

To learn more about the mechanisms and treatment of PGAP3-congenital disorder of glycosylation, watch the dedicated Osmosis video on YouTube and Osmosis.org 

Meet the Landmans

Lucy Landman is one of only a few children known worldwide to have the genetic disorder PGAP3-Congenital Disorder of Glycosylation. Luckily for Lucy, her parents Geri and Zach Landman are both physicians whose expertise has been a big help in obtaining a diagnosis and in advocating for her. The Landmans are bringing that know-how and a fervent desire to help all children with single gene disorders to the non-profit they founded, Moonshots for Unicorns, which is already working with Nationwide Children’s Hospital on a promising gene therapy.  “There are so many of these single gene disorders that should be amenable to things like gene therapy and drug repurposing. So, we don't want this just to focus on PGAP3.” 

Listen to this moving episode with host Michael Carrese to learn what causes PGAP3, how the rare genetic disorder has impacted Lucy’s life and health, and the suspected connection between PGAP3 and Autism. Dr. Landman also addresses the big gaps she sees in newborn screening, medical education and research efforts from a rare disease perspective.

Bonus: Watch the Landman’s take the #HotShotChallenge to raise awareness for single-gene rare diseases.

Organization Taking Strides

Moonshots for Unicorns was born out of the personal tragedy faced by the Landman family, who tell their story in the Raise the Line Podcast episode above. Motivated by their daughter Lucy's diagnosis and refusing to succumb to despair, the couple embarked on a journey to find a cure and help other families in similar situations. They established the nonprofit organization whose name reflects their ambition to achieve what seems impossible, akin to aiming for the moon.

Their mission isn't limited to finding a cure for PGAP3 but extends to other single gene disorders as well, alluding to the broader vision of helping multiple families affected by such conditions. This dedication led to numerous meetings with global doctors, scientists, and pharmacy CEOs. They recognized the potential of gene therapy for treating ultra-rare genetic disorders like PGAP3. However, the rarity of these conditions results in a lack of market demand for treatments. The organization hopes to raise $2.5 million to develop a treatment for Lucy’s disease. Visit their website to lend a helping hand.