Rare Diseases - Hope for a Brighter Future | Tinatin Tkemaladze | TEDxTSMU
A clinical geneticist states that rare diseases, though rare individually, collectively affect 300 million people, many of whom lack diagnosis or approved treatment. He illustrates this crisis using two children, Kira and Elvin, who died from ADA immunodeficiency—a treatable condition—because newborn screening in Georgia does not test for it. The core message is that improving diagnosis through awareness, screening, and global collaboration is critical, echoing the saying that *"diagnosis delayed is life denied."* ## Speakers & Context - Clinical geneticist (speaker) — professionally discusses the challenges of diagnosing and treating rare diseases. - Clinic setting — where the speaker examines children with rare diseases. - Georgia — the specific region highlighted where newborn screening does not include immune deficiencies. - London — location of colleagues investigating samples for a child named Murat. ## Theses & Positions - The main goal of a doctor is prevention, diagnosis, and treatment, all depending on achieving a timely diagnosis. - Rare diseases, despite being rare in incidence, are a large collective problem affecting approximately 300 million people. - Statistically, 95% of rare diseases currently have no approved treatment, and over 80% are caused by gene defects. - The identification of a diagnosis, even if the disease is not treatable, is crucial for preventing recurrence risk in future children. - The study of molecular and cellular mechanisms of rare diseases is the engine that drives precision medicine and future treatments. ## Concepts & Definitions - **Rare disease:** A disease affecting fewer than one in 2,000 individuals; some are "ultra rare" with only a few global cases identified. - **Founder mutations:** Recurrent mutations encountered in small, isolated sub-populations (like the Byanis community in Georgia) that have remained socially and territorially isolated since the 16th century. - **Immodeficiency:** Condition where the body fails to produce sufficient cells to fight even simple bacteria. - **Newborn screening:** Mandatory screening procedures for genetic conditions performed on newborns; in Georgia, this notably *does not* include immune deficiencies. - **Genetic defects:** The primary cause noted for the majority of rare diseases (over 80%). ## Mechanisms & Processes - **Diagnostic Process:** Diagnosis requires analysis of blood samples, which, when showing a mutation, leads to diagnosis of a treatable condition. - **Treatment Success:** Timely therapy and subsequent hematopoetics (like transplantation) can allow children with treatable rare diseases to survive and lead full lives. - **Knowledge Transfer:** Identifying founder mutations in isolated populations suggests that more treatable conditions might go undiagnosed elsewhere. ## Timeline & Sequence - **Kira's case:** Born **2021**; hospitalized at two months for infections; diagnosis of ADA mutation found after one month of lab analysis; parents were notified after the child passed away a week prior. - **Elvin's case:** Born **October 2024**; admitted for infections/poor weight gain; same ADA mutation found; passed away on Sunday; samples shipped Monday. - **MSM1 case:** Successful treatment initiated after genetic testing, with costs covered by charity support for six months, leading to improved skin and hair. Symptoms returned two years after treatment ended due to family poverty. - **Hayam's presentation:** Seen in **October 2024**; initially presented with mild difficulty walking and speech delay. - **Murat's presentation:** Shown as a contrast, being happy and healthy at **seven years** in the video, contrasted with his current state of being paralyzed and unable to talk or walk. ## Named Entities - **ADA:** Specific gene mutated in Kira and Elvin, leading to immunodeficiency. - **MSM1:** Gene mutated in the sister and brother case, leading to developmental delay and skin issues. - **Byanis:** Ethnic minority group from Georgia, historically settled since the 16th century and maintaining cultural isolation. ## Numbers & Data - Prevalence of rare diseases: **Over 6,000** recognized rare diseases. - Prevalence of ADA: One of the **5%** of treatable conditions. - Proportion of rare diseases with no approved treatment: **95%**. - Proportion of rare diseases caused by gene defects: **Over 80%**. - Proportion of rare diseases manifesting in childhood: **75%**. - Mortality rate among children with these diseases: **30% never reach their fifth birthday**. - Kira's birth year: **2021**. - Elvin's birth year: **October 2024**. - Time lapse between Kira's diagnosis and passing: **One week**. - Time gap in MSM1 treatment success: **Two years** until symptoms recurred. - Population size of the Byanis community: Implied small and isolated. ## Examples & Cases - **Kira and Elvin:** Two children who died from ADA immunodeficiency because newborn screening in Georgia did not test for it. - **The Sister and Brother:** Presented with developmental delay, skin manifestations, and alopecia; diagnosis of MSM1 led to improvement after specialized supplement treatment, which ceased due to financial inability. - **Hayam:** Child seen in **October 2024**, presenting with mild difficulty walking and speech delay. - **Murat:** Shown contrastingly healthy at **seven years** enjoying a pool, compared to his current state of being paralyzed. ## Tools, Tech & Products - **Blood test/Genetic analysis:** Lab technology used to identify mutations in genes like *ADA* and *MSM1*. - **Newborn screening:** The screening process that currently fails to test for immune deficiencies in Georgia. - **Special cholesterol supplement and prepared ointment:** Treatment utilized for the MSM1 mutation case. - **Hematopoetics/Transplantation:** Therapeutic procedures that allow survival for treatable rare diseases. ## References Cited - No specific books, papers, or external authors were cited, only references to professional scientific findings (e.g., *ADA* pathway, published case in **2023**). ## Counterarguments & Caveats - The speaker notes that even when a disease is not treatable, parents still seek diagnosis to understand the condition's name. - The speaker acknowledges that the struggle for diagnosis is often one of *timing*, as in the case of Kira and Elvin. ## Conclusions & Recommendations - Global public and healthcare awareness regarding rare diseases must be raised. - Expanding newborn screening protocols to include immune deficiencies is a necessary immediate step. - Support for treatment access and global collaboration are essential to save lives. - Actionable principle: *“diagnosis delayed is life denied.”* ## Implications & Consequences - Missed diagnosis of treatable rare conditions means irreversible loss of life and potential for curative intervention. - The undiagnosed population represents a vast, untapped area for genetic research, driving precision medicine. - Failure to diagnose means parents cannot prevent recurrence risk through proactive measures. ## Verbatim Moments - *"A disease is called rare when it affects fewer than one in 2,000 individuals."* - *"These are the children with rare diseases."* - *"collectively they are common and affect world's 300 million people."* - *"ADA belongs to those 5% of treatable conditions where we have an approved treatment."* - *"On average, diagnosis takes on average six years."* - *"These are the children with rare diseases."* - *"We call it founder mutations."* - *"diagnosis delayed is life denied."* - *"Together we are strong. Together we will save lives."*