Late-Onset GM2 Gangliosidosis Patient-led Listening Session - Objective and Patient Perspectives

Sep 27, 2026

Uploaded by acoobca

Patient-led Listening Session materials from the National Tay-Sachs & Allied Diseases Association (NTSAD) on Late Onset GM2 Gangliosidosis (Sandhoff and Tay-Sachs). The session objective covers understanding disease burden and symptom progression, heterogeneity in onset and presentation, and considerations for drug development. Clinical context is provided for LOTSS, including biological pathway, motor impact, and cognitive/executive challenges. Patient speakers describe early confusing symptoms, long diagnostic delays, and varied progression affecting work, speech, mobility, and daily navigation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Objective of session

Clinical overview of LOTSS

Early onset of symptoms before diagnosis

Journey to diagnosis

Range of symptoms and progression

National Tay-Sachs & Allied Diseases Association (NTSAD) Late Onset GM2 Gangliosidosis (Sandhoff and Tay-Sachs) Patient-led Listening Session January 15, 2021 PATIENTS AND NTSAD NATIONAL TAY-SACHS & ALLIED DISEASES ASSOCIATION Objective of session To provide an understanding of Late Onset GM2 Gangliosidosis (Tay Sachs and Sandhoff), burden and symptom progression, heterogeneity of Late Onset GM2, and potential issues related to drug development Sue Kahn, Executive Director, NTSAD Ms. Kahn opened the session with an introduction to NTSAD, the family community and how NTSAD support adults affected by Late Onset Tay-Sachs and Late Onset Sandhoff disease (LOTSS) . Dr. Cynthia Tifft, Deputy Clinical Director, NHGRI (NIH) Dr. Tifft presented slides giving a clinical description of LOTSS, including the biological pathway and the heterogeneity of both the symptomatic onset and progression of Late Onset Tay-Sachs and Sandhoff diseases, in comparison to the infantile and juvenile onset forms of these diseases. She narrated two videos that demonstrated how the disease deteriorates the anti-gravity muscles, i. e. the triceps and the quadriceps. It does not affect the biceps and hamstrings. She explained that LOTSS patients have normal IQ’s, but there can be challenges when it comes to executive functioning. Speech is pressured and there is dysarthria. The progression of the disease impacts the brain, specifically the cerebellum. Uneven surfaces are very difficult for LOTSS individuals to navigate. She stressed the key challenge with LOTSS, in addition to it being rare, is that the age of onset is variable as are the progression and symptomatic presentations. The advantage is that there are natural history studies that show impact on gait, balance, and fine motor skills. There are animal models – mouse, cat, and sheep. There are biomarkers. There is an established LOTSS Think Tank with 20 investigators actively involved. There are patients who are incredibly motivated to find treatments and cures. Members from the NTSAD Late Onset community ranging in ages from 32 to 55 agreed to share their perspectives and experiences living with their diagnosis of Late Onset Tay-Sachs and Late Onset Sandhoff diseases. 2 NTSAD NATIONAL TAY-SACHS & ALLIED DISEASES ASSOCIATION Early Onset of Symptoms Before Diagnosis All five patients who spoke about their symptoms could look back at points in time in their childhood and identify symptoms that caused them distress. From unexplainable symptoms to being clumsy to struggling with their speech, they expressed frustration with these confounding symptoms that interfered with their childhood, college experiences and life plans. • “I always wanted to be in the military and later become a police officer just like my father, I knew I would never attain that goal, because of my symptoms I would never pass basic training or the police academy.” • “She is a Wellesley graduate and also has MBA from Santa Clara University. She speaks three languages. However, she cannot work now and on disability.” • “I used to play soccer and other sports. I had a tremor in my hands that appeared around 17/18 years of age. The neurologist prescribed medicine for the tremor. While I was in college, stairs became a problem. It took all of my energy to get up a flight of stairs and the same was true for my twin sister.” • “I was always active, physical, and fast! Played all sports! I always had a speech impediment due to tongue movement. I had speech [therapy] through high school and nothing helped. In college, I became weaker and the thought I was drinking too much, partying too hard in his fraternity….and then started falling down and not knowing why.” Journey to Diagnosis Another common theme was the considerable length of time (ranging from 8 to 30 years) it took them to receive a confirmed diagnosis. • “I’m 55 years old. I was diagnosed in 2014 [nearly 30 years since his diagnostic

FAQs

What is the purpose of the NTSAD patient-led Listening Session?

To explain Late Onset GM2 Gangliosidosis, including burden and symptom progression, heterogeneity of onset and presentations, and potential issues related to drug development.

How does LOTSS typically affect physical and neurological function?

The clinical overview highlights deterioration of anti-gravity muscles (triceps and quadriceps), challenges with balance and gait, and progression impacting the cerebellum and navigation on uneven surfaces.

Why do many patients experience delays in receiving a confirmed diagnosis?

Speakers describe symptoms that were distressing but confounding in childhood and were often attributed to other conditions, leading to long diagnostic journeys ranging from 8 to 30 years.

Sep 27, 2026

Uploaded by acoobca