Rare and Orphan Diseases

Hemophilia A is a rare bleeding disorder caused by deficiency of clotting factor VIII. The current standard of care for patients with severe hemophilia A centers on replacement therapy with factor VIII concentrate, either on demand when bleeding occurs or prophylactically (replacement therapy). Potential complications from replacement therapy include the development of inhibitory antibodies that attack the clotting factor in approximately one-fourth of patients, viral infections from human clotting factors, and bleeding in joints and muscles resulting from treatment delays. According to treatment guidelines from the Medical and Scientific Advisory Council (MASAC), “Inhibitor development is the most severe complication of treatment for patients with inherited hemophilia A.” In addition, the high cost and frequency of infusing factor VIII concentrates can increase the potential for side effects, thereby negatively affecting patient quality of life.

Fortunately, several unique agents have been newly approved or are currently under development. These agents promise to reduce morbidity and improve quality of life for patients. Clinicians will be challenged to integrate these new agents into their clinical practices.

AXIS routinely collects and analyzes data gathered from participants in our live grand rounds programs. These questions provide incredible insight regarding the persistent challenges that clinicians face when …

The month of September is dedicated to raising awareness of sickle cell disease, which affects approximately 70,000 to 100,000 Americans each year. Here to tell us more about this prevalent condition and the various resources available is Dr. Jennifer Caudle.

Five months pregnant, on a flight headed for Hawaii, Allison Pataki's life took a sudden turn when she witnessed her husband, Dave Levy, lose consciousness. After an emergency landing and evaluation, Levy was found to have had suffered a rare stroke.

When he woke the next day, he had amnesia, leaving the young couple holding onto hope for recovery. True to form, Pataki began to write letters to her husband—letters that became the foundation for Beauty in the Broken Places: A Memoir of Love, Faith, and Resilience.

Castleman disease, a rare idiopathic multicentric disorder, is diagnosed in approximately 5000 people in the United States each year. When one 3rd year medical student suddenly found himself facing this diagnosis personally, at a time when knowledge about the disease was minimal, he helped create a broad-based initiative to address this knowledge gap.

Host Dr. John Russell talks with Dr. David Fajgenbaum, a Research Assistant Professor of Medicine in Translational Medicine/Human Genetics and Associate Director of Patient Impact for the Penn Orphan Disease Center at the University of Pennsylvania. He is also co-founder of the Castleman Disease Collaborative Network, a global initiative dedicated to accelerating research and treatment for Castleman disease and improving survival for all patients.

Importance: Understanding the relationship between aneuploidy detection on noninvasive prenatal testing (NIPT) and occult maternal malignancies may explain results that are discordant with the fetal karyotype and improve maternal clinical care.

Objective: To evaluate massively parallel sequencing data for patterns of copy-number variations that might prospectively identify occult maternal malignancies.

Design, Setting, and Participants: Case series identified from 125 426 samples submitted between February 15, 2012, and September 30, 2014, from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening. Analyses were conducted in a clinical laboratory that performs DNA sequencing. Among the clinical samples, abnormal results were detected in 3757 (3%); these were reported to the ordering physician with recommendations for further evaluation.

Exposures: NIPT for …

Over the past decade, Food Protein Enterocolitis, or FPIES, has emerged as the most actively studied non–IgE-mediated gastrointestinal food allergy because of its acute onset, severity of symptoms, and distinctive clinical features. Yet as a rare allergic disorder of infancy and young childhood, it is often misinterpreted and misdiagnosed in clinical practice, leading to difficult treatment paths for patients and their families. Joining Dr. Renee Matthews to present a case history from the vantage point of a patient's mother, including challenges faced in reaching the correct diagnosis and starting effective treatment regimens, is Jennifer Kandt.

An award-winning memoir that goes far beyond its riveting medical mystery, Brain on Fire is the powerful account of one woman's struggle to recapture her identity. When twenty-four-year-old Susannah Cahalan woke up alone in a hospital room, strapped to her bed and unable to move or speak, she had no memory of how she'd gotten there. Only days earlier, she had been leading an exciting life at the beginning of her promising career at a major New York newspaper. Now she was labeled violent, psychotic, a flight risk. What happened?

Susannah's memoir tells the astonishing true story of her descent into madness, her family's inspiring faith in her, and the lifesaving diagnosis of an exceedingly rare disease which led to her complete recovery.

Multivisceral transplant entails the transplant of nearly all the abdominal organs, with the exception of the kidneys. It is a highly unusual procedure, with only about 30-40 such surgeries occurring per year in the United States, compared to thousands of liver transplants performed annually, in only about seven transplant centers in the United States. Host Dr. Aaron Carroll welcomes Dr. Rodrigo Vianna, director of intestinal and multivisceral transplant at Indiana University Health, to discuss when multivisceral transplant can be used to treat patients with rare tumors, such as neuroendorcrine or desmoid tumors.

For the 12 million Americans who suffer from restless leg syndrome (RLS), the disease can often be misdiagnosed and misunderstood. Doctors as well as their patients are now more familiar with RLS due to the intense marketing of drugs used to treat restless legs syndrome. Host Dr. Anthony Alessi talks with Dr. Carl Ansevin, an adjunct faculty member in the department of biomedical sciences at Kent State University and sleep specialist at the Ohio Neurologic Institute in Boardman, Ohio, about how to properly diagnose and treat restless leg syndrome and which patients are more at risk of developing the disease.

Only a few years ago familial dysautonomia (FD) was a fatal disease, but some "Rediscovery Research" from the FD lab at Fordham University in Bronx, New York, is turning this killer into a chronic manageable disease. What have we learned from familial dysautonomia research, and how might this help patients with other diseases? Joining host Dr. Bruce Bloom to provide an update on current FD research and treatment is Dr. Berish Rubin, professor in the department of biological sciences and head of the laboratory for familial dysautonomia research at Fordham University.