Understanding CerTra Syndrome
CerTra Syndrome is a rare genetic disorder that profoundly impacts the lives of those affected and their families. It manifests in various debilitating symptoms, often requiring comprehensive medical care and support. At Lottie’s Light Foundation, we are dedicated to advancing research and providing resources to improve the quality of life for those living with this condition. Our goal is to foster a community of support and hope, driving forward the search for a cure.
What is CerTra Syndrome?
(A high-level overview)
In brief, the mutations that cause CerTra lead to over-production of certain lipids, leading to dysfunction in many cell types. The result is that early cognitive, physical, and emotional development are affected to greater or lesser degrees, depending on the mutation.
What are the symptoms of CerTra Syndrome?
As of May 2024, only a few dozen cases of CerTra Syndrome have been identified. Based on this very small number of patients, we can say that mutations in CERT1 typically cause some degree of the following:
Neurologic symptoms
- Intellectual disability
- Seizures
- Disrupted sleep patterns
- Autistic-like traits
- Ability to stare into your soul and know everything you’re thinking*🦄
- A few individuals have developed visual (CVI)* or auditory deficits
- High pain tolerance (which can lead to self-harm or at least lack of awareness of injury)
Motor symptoms
- Speech delay
- Feeding difficulties
- Hypotonia
- Sitting, crawling and walking delays
Physical symptoms
- Mild skeletal abnormalities such as syndactyly (when two fingers are fused or webbed), club foot, or hallux varus (where the big toe deviates to the side).
- Unibrow
- Gap in teeth
- Beautiful, bright and stunning smile*🥰
Sources: https://www.jci.org/articles/view/165019/sd/1 and parent reported*
What causes CerTra Syndrome?
You may already know that lipids such as phospholipids and cholesterol are abundant in the central nervous system, where they help form the membranes that determine which molecules can enter and exit the cell. Sphingolipids are more involved in cell signaling, wherein cells respond to cues that indicate whether they should proliferate, differentiate, migrate, mount a stress response, or end their life cycle.
Ceramide is the backbone of all sphingolipids. The CERT1 protein transports ceramides, so it plays a key role in maintaining the right amount of sphingolipids to serve the cell’s ever-changing needs. The mutations that cause CerTra disrupt CERT1’s ability to regulate sphingolipid homeostasis, so too much gets produced. The excess sphingolipids then overwhelm the cell.
There are other genetic diseases that involve defects in the production and degradation of sphingolipids, but from different causes and in different tissues. Recent research has even found that aging-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s involve the accumulation of ceramides. Clearly, ceramide and sphingolipid levels must be very precisely controlled throughout the lifespan.
How many people have CerTra Syndrome?
*As of October 2024
Is there a treatment for CerTra Syndrome?
We are actively pursuing the development of drugs and therapuetics that reduce the activity of CERT1 therfore treating and curing CerTra Syndrome.
What research is being done today for CerTra Syndrome?
Researchers have three major goals:
- To better characterize the features of the disease and identify more patients so that we can get reliable information on the natural history of CerTra
- To understand how specific mutations lead to specific problems in development, and whether certain genetic or environmental factors influence how CerTra affects a given individual
- To understand why different mutations seem to have different effects or degrees of severity