Patient Presentation
A pediatrician was talking with her brother who said, “Do you mind if I ask you a medical question?” Slightly hesitantly she said “okay.” He went on, “I have someone I work with closely and his 3-year old boy started having some medical problems, and then recently he had a seizure and was admitted to the children’s hospital. I don’t know a lot more than that but they diagnosed him with something called Tay-Sachs disease. I looked it up and it looks pretty scary to me. I just wondered if you know anything about it? I’m not trying to be nosy. He’s a great guy to work with, and, I guess I just want to understand better.” “I know you and you’re not that type. You’re a listener not a blabber. You want to know so you can listen better to him, right?” she asked. “Yeah, I just think if I understand it better then maybe he wouldn’t have to explain everything if he wants to talk,” said the brother. “Well Tay-Sachs is not something I usually take care of. It’s a problem where there is an enzyme that doesn’t break down the chemicals in the cells right. Those buildup in cells and in the organs, especially the brain and the build up can cause problems. That is probably the reason the boy had a seizure. I know there are different types depending on when the symptoms show up. What they really teach us in medical school is the classic type that affects babies in the first year of life. They have short life spans. Since the little boy is older than that, it’s likely a little different than the baby type, but I would have to look it up and see more exactly what the life span is and any specifics about it. I just remember that all the patients have neurological problems and shortened life spans but obviously that varies alot depending on the person. They also have a specific eye finding which used to help make the diagnosis especially before we had other testing.” Does that sort of help?” she asked. “Yeah, that is sort of what I read, but hearing you say it helps me,” he replied. “I’m very sorry for your friend. It’s a hard diagnosis. I’d also say that the children’s hospital personnel should be able to help him and his family. I’m not sure I can be of any direct help, but if you need some more information I can try to help you understand,” she answered.
Discussion
Tay-Sachs Disease (TSD) is one of many lysosomal storage disorders (LSD). LSD are a group of heterogeneous, monogenetic disorders in which there is disruption of the normal biochemical processes within the cellular lysosome. Toxic waste accumulates within the lysosome which causes “…irreparable cellular damage and organ dysfunction followed by premature death.” Most patients present in infancy or childhood with progressive neurological symptoms. There are some enzyme replacement therapies for some diseases [Gaucher Disease was the first and more information about Gaucher can be found here], but the blood-brain barrier is a significant hurdle for central nervous system-targeted treatment. Some other LSDs may also be treated with stem-cell transplantation.
Each LSD is rare but in combination they have an incidence rate of ~ 1:7-8000 live births. Most are autosomal recessive but some are X-linked (e.g. Mucopolysaccharidoses Type II). Newborn screening tests for many LSDs and also prenatal counseling and specific disease testing may be offered to persons with a high-risk of specific LSDs. Some of the more common LSDs include Batten, Fabry, Gaucher, Krabbe, Niemann-Pick, Pompe, Metachromatic Leukodystrophy, Mucopolysaccharidoses, Sandoff, Tay-Sachs and Wolman.
Learning Point
Tay-Sachs Disease is considered a HEXA disorder because the enzyme hexosaminidase A is used to degrade GM2 ganglioside. Without this enzyme, GM2 ganglioside builds up especially in brain and nerve tissues. It is autosomal recessive and there is a higher risk for the genetics within certain Jewish, Cajun and French Canadian populations. Treatment is supportive, along with genetic counseling.
TSD has 3 subtypes:
| Subtype | Acute Infantile | Subacute Juvenile | Late Onset | |
|---|---|---|---|---|
| Age of Symptom Onset | 3-6 months | 2-5 years | Teens – adulthood | |
| Major Neurological Symptoms | Progressive weakness and motor skill loss, myoclonic jerks | Normal development, then plateauing, then developmental skill loss | Progressive antigravity muscle weakness especially of lower extremities | |
| Other Neurological Symptoms | Cherry-red spots on macula, exaggerated startle response, decrease attentiveness and unusual eye movements, hypotonia, hyperreflexia and sustained ankle clonus | Retinal pigmentation can be seen later in disease, increased muscle spasticity and decrease ambulation, speech declines from dysarthria and drooling to absent speech | Frequent falls, incoordination, dysarthria, tremor | |
| Seizures | Approximately 12 month age onset | Onset during this time period | Psychiatric problems, memory and executive function problems are more common | |
| Neuroimaging | Progressive macrocephaly and ventricular enlargement | Progressive global brain atrophy | Isolate cerebral atrophy | |
| Progression and Life Span | Relatively rapid deterioration with lifespan being age 2-3 years in general, sometimes supportive cares prolong to 5-7 years | Slower deterioration but lifespan is to age 10-15 years | There is a broad clinical variation |
ClinicalTrials.gov is one clearinghouse for patients and families who may be looking to participate in all types of research studies including Tay-Sachs disease.
Questions for Further Discussion
1. What has been your experience with taking care of and supporting families with rare diseases?
2. What online resources are available with quality information about rare diseases?
3. How do you handle family and friends who ask you for medical information or advice?
Related Cases
- Disease: Tay-Sachs Disease
- Symptom/Presentation: Genetic Disorder | Seizures
- Specialty: Developmental Disabilities | Genetics | Neurology / Neurosurgery
- Age: Preschooler
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for these topics: Tay-Sachs Disease and Lipid Metabolism Disorders.
To view current news articles on this topic check Google News.
To view images related to this topic check Google Images.
To view videos related to this topic check YouTube Videos.
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Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa