1 – International registry and biorepository.
Abetalipoproteinemia and related disorders are poorly understood ultra-rare diseases that are frequently met with suboptimal treatment. The Abetalipoproteinemia & Related Disorders Foundation recognized that an international registry to identify patients for clinical studies and a biorepository to identify biomarkers associated with disease progression would facilitate new treatment modalities.
In this regard, Dr. Mahmood Hussain from NYU Grossman Long Island School of Medicine is working on a promising project for the ABL+ community. He has received permission from the university to start a bioregistry and a biorepository for ABL/FHBL/CMRD patients. It is expected that a better understanding of the pathophysiology and management will significantly reduce the medium and long-term repercussions of these diseases, and simultaneously will increase patient’s quality of life. Furthermore, a consistent database can potentially boost engagement from the medical and research communities, attracting more resources for further recommendations and new studies as well. So, if you are an ABL/FHBL/CMRD patient or a caregiver (in any country in the world) interested in participating in this project, please send an email to mahmood.hussain@nyulangone.org or michele.heidenfelder@nyulangone.org. It will be very valuable and Dr. Hussain and Mrs. Heidenfelder will gladly return guidelines. We want to establish a robust bioregistry. Please send pertinent information about your disease and mutations to them. A robust registry can help us advocate for the betterment of our community. We understand that participation in biorepository might be difficult because you need to visit in person. However, for any reason, you happen to be in New York, please reach out to us we will work with you to facilitate collections of blood and saliva for the biorepository. Although, we are still in infancy, based on the early participation of some of our patients in our bioregistry, we have already identified a novel missense mutation in the MTTP gene in one patient. This missense mutation (I344N) abolishes the interaction of the MTP subunit with the PDI. This results in loss of all the lipid transfer activities of MTP. Hence, this MTP is unbale to help in the assembly of apoB-containing lipoproteins, therefore, causing ABL. More participation by our community in the bioregistry may help us understand structure-function of genes involved in lipoprotein assembly and secretion.
2 – Adding ABL/FHBL/CMRD to the Recommended Uniform Screening Panel (RUSP).
The RUSP panel is a blood test administered to babies at birth looking for 35 rare diseases, but the three diseases the ABL+ Foundation is concerned with are not on the panel. Also, the panel is not in use in every state in the USA. Patients and caregivers are well aware of the arduous journey it takes to confirm the diagnosis of ABL/FHBL/CMRD. This process requires a high financial and emotional cost. Furthermore, the longer this process takes, the more severe the repercussions of the disease will be. On the other hand, patients diagnosed early may not develop any harm to their health, because these illnesses are treatable and if managed correctly the damage caused by the vitamin deficiencies related to these disorders can be substantially mitigated. So, we can imagine how much better it would be if the diagnosis was known at birth! To this end, Dr. Mahmood Hussain is working on adding ABL/FHBL/CMRD to the RUSP.
The first few weeks are very distressing for parents and patients with these diseases: a long-awaited great moment in their lives, but parents become agonized day by day seeing that their baby is not gaining weight, accumulating several other bad repercussions. The diagnosis confirmed at birth will definitively rule out so many painful situations.
A critical reason for including ABL/FHBL/CRMD in the Screening Panel is the severity of these diseases, shortened lifespan subsumed. A real scenario of the incidence of these diseases will be obtained if Dr. Hussain’s project is approved, leading to more attention from health professionals and resources for researchers.
Access to X-ALD newborn screening database in New York State. Working with Dr. Shahidul Islam, Dr. Hussain has been successful in gaining access to X-ALD NBS database in the New York State. Preliminary studies indicate that there are few samples with very low VLCFAs in this database. A thorough analysis of the past five years’ data is underway. This analysis is likely to provide evidence for proof-of-the-concept that hypolipidemia ABL/FHBL/CMRD patients, will have low levels of VLCFAs and can be identified during the screening of X-ALD.
3 – Multimodal retinal imaging of abetalipoproteinemia.
Two ABL patients have volunteered for multimodal retinal imaging at the Vitreous Retina Macula Consultants of New York. This resulted in state-of-the-art visualization of changes occurring in the eyes of these patients. This study has been reviewed by the Ophthalmic Genetics journal and a revised manuscript has been submitted. It is likely to be accepted for publication.