Yale School of Medicine Receives Philanthropic Gift from Grateful Family to Establish the Yale Transketolase Deficiency Program and to Advance Research on Rare Disease

Harriet Schleifer, JD, (retired), and Leonard “Len” Schleifer, MD, PhD, first sensed something was amiss with their son David when he was just 2 weeks old. Like many parents, they held expectations of typical developmental milestones—the first smile, the first step, the first word. However, David seemed different. As one pediatrician told Harriet, “David is special.”

David, now 39 years old, struggled to engage with his surroundings in a way that left the Schleifers concerned. Cognitive issues as well as speech and learning disabilities became increasingly apparent. These early signs, coupled with their parental intuition, set them on a journey to uncover the deeper issues affecting their son.

The Schleifers’ 30-plus-year quest led them to ultimately undergo extensive gene and DNA testing at the Yale Neurogenetics Clinic, where their consultations with David’s physicians—Andrew Wang, MD, PhD, associate professor of internal medicine (rheumatology) and of immunobiology, and Anna Szekely, MD, RES ’97, RES and FEL ’99, neurogeneticist, assistant professor of neurology—provided the answers they sought.

Through the genetic evaluation and sequencing work of Szekely six years ago, David was diagnosed with transketolase (TKT) deficiency, a rare autosomal recessive hereditary and metabolic disease involving a defect in the enzyme TKT, which is crucial for cellular energy production and the synthesis of nucleotides. Recent studies have shown that TKT deficiency is closely associated with inflammation and dysregulation of T cells and appears to be most common among Ashkenazi Jews. With only approximately 11 known cases worldwide, TKT deficiency is often underrecognized and poorly understood. The Schleifers hope to change that with their gift.

To show appreciation for Wang, Szekely, and David Hafler, MD, William S. and Lois Stiles Edgerly Professor of Neurology, professor of immunobiology, and former chair of the Department of Neurology at Yale School of Medicine (YSM), and to help ensure that YSM has the resources needed to advance its research while increasing awareness of TKT deficiency, the Schleifers made a philanthropic gift to establish the Yale Transketolase Deficiency Program.

“Drs. Wang and Szekely have been my lifesavers at Yale,” says Harriet. “It is because of them that Len and I gave a gift to launch the Yale Transketolase Deficiency Program.”

The Schleifers’ gift to YSM will support groundbreaking studies, the development of new therapies, and comprehensive clinical care initiatives focused on TKT deficiency.

“I was immensely grateful and honored when Harriet and Len told us of their intentions to support TKT research at Yale,” says Wang. “It’s a real testament to their commitment to advancing science and health care.”

“Harriet and Len’s generous support exemplifies a key mission in rare-disease research, care, and advocacy,” adds Szekely.

Harriet grew up in the Bronx and Queens, N.Y., the daughter of two Holocaust survivors. “My father was the sole survivor of his family, and my mother lost her entire family except for one brother. Everyone else was transported to the Treblinka extermination camp,” says Harriet.

Her parents immigrated to the United States in 1947, having been sponsored by an aunt of her father who had come to the U.S. prior to World War II. “My father had no education, no money, and didn’t speak any English,” she says. “I grew up in a home that had a lot of history and challenges while appreciating hard work. Although we had experienced sorrow, we had no bitterness. We appreciated life and people. Family is precious.”

Harriet’s father started a slipcover business and later a factory that made quilting and batting. “He worked very long hours and on weekends and was committed to taking my sister and me to the park, to the botanical gardens, and ice skating,” she shares.

Harriet earned a bachelor of science degree from Cornell University, two graduate degrees in education from the University of Virginia, and a law degree from St. John’s University. She practiced law with a focus on education law, advocating for students with special needs. She serves on the executive committee of Cornell University, the executive committee of Chapel Haven Schleifer Center, and has held top leadership posts in national Jewish organizations including the Conference of Presidents of Major American Jewish Organizations and American Jewish Committee.

Len was also raised in Queens. He earned a bachelor of arts degree from Cornell and his MD and PhD in pharmacology from the University of Virginia. In 1988, he co-founded Regeneron Pharmaceuticals, a biotechnology company, and serves as its board co-chair, president, and chief executive officer. His personal mission in life is “to do well by doing good.”

Throughout his life, David has suffered from a host of medical conditions, including neurodevelopmental delay affecting cognitive, language, and fine motor functions, early feeding difficulties, delayed growth with short stature, digestive and pancreatic issues, orthopaedic challenges, and joint pain. He was born with hip dysplasia, and at 39, stands 5 feet tall. He had strabismus as an infant, cataract surgery when he was in his teens, and later developed uveitis. David’s facial features appear “impish.” As a child, he was both hyperactive and hyperfocused; he is still hyperfocused on particular things. He is also very endearing.

Over the years, the Schleifers faced an array of unanswered questions. Initial assessments, genetic testings, and consultations (including searching through photo albums of other children with special needs to see if David resembled any of the other subjects) did not point to any etiology of his various, seemingly disparate problems.

The turning point in the Schleifers’ journey came when Szekely evaluated David on the recommendation of Hafler, and she conducted genome-wide sequencing at the Yale DNA Diagnostic Laboratory. Len, a trained neurologist, and Harriet had wondered if an undiagnosed genetic condition could explain David’s difficulties. Szekely’s comprehensive approach provided a definitive clinical and molecular diagnosis: David has TKT deficiency.

Szekely’s diagnosis provided the Schleifers with the clarity they had long sought and set the stage for targeted and meaningful intervention.

Szekely’s passion for neurology and genetics propels her commitment to advancing patient care through both basic and translational research. Similarly, Wang’s dedication to understanding the biochemical pathways altered by TKT deficiency is vital in developing potential interventions and novel therapies to mitigate the disease’s effects.

Their collaboration and the establishment of the Yale Transketolase Deficiency Program represent a concerted effort to address the needs of patients like David through innovative research and comprehensive clinical care.

The mission of the Yale Transketolase Deficiency Program is to provide state-of-the-art comprehensive medical care to patients with TKT deficiency, perform multidisciplinary cutting-edge research to understand the disease’s pathogenesis, and develop new therapies to improve the lives of patients with TKT.

The program focuses on the following areas:

• Recruit patients with TKT deficiency to understand the full spectrum of the condition.
• Provide long-term, high-quality care through multiple subspecialists.
• Use advanced molecular technologies to conduct basic research, including to identify additional genetic modifiers that may influence the disease and understand the disease mechanism by single-cell sequencing of affected cell types in TKT deficiency.
• Collaborate with a wide network of health care partners to increase awareness and improve diagnosis rates.

The Yale Transketolase Deficiency Program seeks to collaborate with broader initiatives at Yale, such as research on inflammation biology and rare-disease hubs within the Undiagnosed Diseases Network and the National Organization for Rare Disorders. These partnerships enhance the program’s impact through shared knowledge and resources, fostering a robust understanding and treatment framework for TKT deficiency.

The Schleifers’ commitment extends beyond providing care for David; they actively work to identify and support other individuals and families affected by TKT deficiency. By raising awareness and promoting early diagnosis, the Schleifers hope to prevent other families from experiencing the prolonged uncertainty they once faced.

Although TKT deficiency appears to be prevalent among Ashkenazi Jews, research has shown that there are other variants that have not yet been fully identified in the patients with different ancestries. “We’ve identified the variant that seems to run in the Jewish population,” says Harriet. “But there are more ways for TKT to appear, and there could be a population affected that we’re not aware of. We also need to identify the extent and how widespread the carrier rate is.”

Each month, she, Wang, and Szekely meet with a group of parents to discuss the latest TKT news, connections, and efforts. Harriet shared that she has begun relationships with other genetic screening and medical research institutions involved in rare genetic diseases, including one in Israel, to help “move the knowledge forward.”

“I’m impressed by the scope of Harriet and Len’s future vision, including understanding the unknown prevalence of this condition worldwide and their commitment to implementing various forms of screenings, such as preconception genetic testing and ultimately, newborn screening,” says Szekely.

Wang and Szekely stressed the vital role of philanthropy in advancing rare-disease research.

“As interest in supporting scientific research and academic medicine is changing, there is no more important time than now for philanthropy,” says Wang. “Beyond advancing basic biology and clinical care of TKT deficiency, Harriet and Len are also supporting several early- and mid-career scientists and doctors across four departments (internal medicine, neurology, immunobiology, and ophthalmology) as part of the TKT research team. Support of young scientists and doctors is necessary for the flourishing of our society. We are enormously grateful for their selfless commitment to science and medicine.”

Szekely agrees. “With technological advances, the number of identified rare genetic disorders is rapidly increasing. Understanding these diseases, caring for these patients, and developing specific therapies would not be possible without the vision and support of extraordinary donors like the Schleifers.”

Reflecting on Len’s and her inspirations for giving to YSM, Harriet shared the wisdom of Rabbi Hillel the Elder: “If I am not for myself, who will be for me? If I am only for myself, what am I? If not now, when?”

Harriet reinforced their commitment with her own philosophy: “If you can, you must contribute. If you have the privilege to help someone, then you must. If you want society to be even better, you have to invest in it.”