Late-Onset Tay-Sachs Disease (LOTS) and Sandhoff Disease (LOSD) have a variety of different symptoms, which can affect mobility, coordination, cognition, and behavior, resulting from abnormal accumulation of GM2 GangliosideA fatty substance or lipid that is part of normal metabolism, in Tay-Sachs and Sandhoff lack of enzyme function causes the GM2 gangliosides to accumulate which is toxic and eventually causes cell death. Tay-Sachs and Sandhoff are known collectively as GM2. More in the nervous system.

In some patients, psychiatric symptoms can be early and very disabling manifestations of the disease.

Psychiatric symptoms appear to be common in younger LOTS patients and are rare in LOSD.

The medical literature in Late-Onset GM2 Gangliosidoses suggests that between 30 to 50% of young patients with LOTS may develop severe psychiatric symptoms. How GM2 accumulation (especially in LOTS) might result in psychiatric symptoms in unknown.

There are two typical forms of psychiatric manifestations in GM2 Gangliosidoses:

Mood Instability, which can mimic symptoms of bipolar affective disorder (manic depression) and in some cases, episodes of “Mania”. Symptoms include severe insomnia (difficulty sleeping), hyperactivity / excess energy, euphoria / extreme excitement, grandiose ideas, risk-taking, agitation, disinhibition, and poor judgement lasting days to months.  This elevated mood state might alternate with symptoms of depression, including sadness and tearfulness.

Thought Disorder, or “Psychosis”, which can mimic schizophrenia. The symptoms involve patients experiencing a distorted and unreal perception of reality, including delusions (falsely held beliefs, which are unshakeable), and hallucinations (seeing, hearing, or feeling things that are not there).

These two main categories represent serious medical and psychiatric conditions that require rapid evaluation and treatment, to promptly restore baselineBaseline is a technical term for “the new normal” or how things looks when they are stable. With Tay-Sachs, Canavan, GM1 gangliosidosis, and Sandhoff diseases, the baseline shifts, and often it shifts down over time like steps, where each lower step represents a lower level of functioning. More mental state and function, minimize risk of injury, and prevent recurrence.

Currently, these symptoms are managed by psychiatry clinicians, including psychiatrists and therapists, following general guidelines.

Depending on individual circumstances, a host of interventions are available to manage patients presenting with Mania and/or Psychosis, including medications to control abnormal thoughts and behaviors and, in severe cases, electroconvulsive therapy (ECT) has been tried.

While the medical literature is quite limited, there is a report suggesting that older “first-generation” anti-psychotic medications (sometimes referred to as neuroleptics), which strongly block the neurochemical dopamine, could, at least temporarily, worsen the motor and other symptoms in patients with LOTS. There is very limited data in LOSD.

The choice of treatment of psychiatric symptoms should be carefully crafted on an individual basis in coordination with a psychiatrist/behavioral health specialist and the neurologist, ensuring that all healthcare team members are aware of the patient’s history of GM2 Gangliosidosis.

Information on Psychosis from the National Institutes of Health can be found below:

https://www.nimh.nih.gov/health/publications/understanding-psychosis

Information on Bipolar affective disorder and Mania from the National Institutes of Health can be found below:

https://www.nimh.nih.gov/health/publications/understanding-psychosis

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