
At the Harvard 2024 Rare Disease Hackathon this past March, Paul Biderman and Dr. Cindy Bredefeld represented the ABL+ Foundation and met with Caltech undergraduate Yoyo Benchetrit, who is studying biology and chemistry. This event introduced Yoyo to abetalipoproteinemia (ABL) for the first time.
After speaking with Dr. Bredefeld, Yoyo shared: “I was able to learn how ABL is unique compared with other rare disorders in the sense that there is a treatment/management plan for the disease, but having a diagnosis and early intervention in childhood is the major challenge. I think the event and learning from Dr. Bredefeld and Paul really shed light on how unaddressed needs in our medical system encompass under-diagnosis for under-researched/rare disorders like ABL, which is why I was inspired to continue to learn how to improve recognition of ABL and reached out to Paul and Dr. Hussain following the event.”

From working with Dr. Hussain and Dr. Bredefeld, Yoyo soon became aware that one factor contributing to ABL’s under-diagnosis is its exclusion from newborn screening panels, likely due to the disorder’s rarity combined with economic factors. As a result, she has been collaborating with Dr. Bredefeld and Dr. Hussain to work on a review to facilitate earlier diagnosis for ABL patients by piggybacking off another disorder, X-linked adrenoleukodystrophy (X-ALD).
That is, Dr. Bredefeld and Dr. Hussain found from the fatty acid profiles of a couple of ABL patients, that they appear to have lower levels of very long-chain fatty acids (VLCFAs). As a result, it is possible that there is a correlation between low VLCFAs and ABL. In the case of X-ALD, which is a disease that is tested for in state newborn screening panels, there are high levels of VLCFAs (contrasting with the apparent low levels seen in ABL patients). So, they are trying to provide evidence that when newborns are screened for X-ALD and their VLCFAs are tested for, that patients with low VLCFAs should be flagged for follow-up genetic testing for ABL.
This approach could lead to earlier intervention for ABL without the need to add it as a separate condition on screening panels. Currently, the team is working on a draft of the paper, with efforts underway to gather more fatty acid profile data from ABL patients and explore access to newborn screening data.
Beyond this project, Yoyo is keen to explore novel treatment mechanisms for ABL. At Caltech, she is involved in developing gene therapy tools for neurological disorders and is investigating how these could be applied to ABL. Specifically, she aims to leverage her work with induced pluripotent stem cells (iPSCs) and gene therapy to deliver a functional MTTP gene to the intestine, where apoB-48 is synthesized, to restore apoB-48 protein expression.
If successful, these model systems could not only enhance our understanding of fat-soluble vitamin absorption in ABL patients but also lead to improved delivery methods to enterocytes. With a deep interest in gene therapy, Yoyo plans to carry this work forward into medical school, continuing her commitment to innovative solutions for complex diseases.
As Yoyo’s journey with ABL+ Foundation continues, her collaborative efforts highlight the importance of early intervention, advocacy, and innovative research to improve the diagnosis and management of rare disorders like ABL.