Symptoms and Progression of HDL1

Because Huntington disease-like 1 (HDL1) is so rare, its symptoms can vary widely. It is common for two people with the same genetic mutation—even within the same family—to have very different experiences ^[1]. Understanding the range of possible symptoms can help you prepare for changes and ensure you are getting the right support from your medical team.

Movement (Motor) Symptoms

The motor symptoms of HDL1 often resemble those of Huntington’s disease. You may notice a mix of movements that are too fast or too slow ^[2].

• Chorea: These are involuntary, irregular, dance-like movements that can affect the face, trunk, or limbs ^[2].
• Bradykinesia: A general slowing of physical movement. Tasks that used to be quick, like buttoning a shirt, may take much longer ^[2].
• Myoclonus: Brief, shock-like jerks of a muscle or group of muscles ^[3].
• Ataxia: A lack of muscle coordination that can cause clumsiness, loss of balance, or an unsteady, poorly coordinated way of walking ^[3].
• Aphasia and Mutism: Changes in speech and communication can occur. Aphasia is an impairment of language, such as difficulty finding or understanding words. In later stages, some individuals may develop a syndrome called akinetic mutism, which is a profound reduction in spontaneous movement, speech, and initiation (not merely a loss of the ability to speak) ^[4][3]. Not every person develops these conditions or follows this sequence.

Thinking (Cognitive) and Mood Symptoms

Changes in the brain’s “prion proteins” also affect how a person thinks, feels, and behaves.

• Dementia: This refers to a decline in memory, reasoning, and the ability to perform daily tasks ^[2].
• Personality Changes: You may notice shifts in temperament, such as increased irritability, apathy (lack of interest), or impulsivity ^[2].
• Psychiatric Symptoms: Some individuals may experience severe agitation, severe depression, or psychosis, which can include hallucinations (seeing things that aren’t there) or delusions (strongly held false beliefs) ^[5].

Understanding the Timeline

One of the most challenging aspects of HDL1 is its unpredictable timeline. In the small number of families studied, the disease duration—the time from the first symptom to the end of life—has ranged from as short as 3 months to more than 20 years ^[2].

While some forms of prion disease are known for being extremely rapid, HDL1 can often follow a much slower, “Huntington-like” course over a decade or more ^[5]. Your medical team will monitor you closely to understand your specific “pace” of progression.

When to Seek Urgent Care

While many symptoms of HDL1 are managed during regular neurology appointments, some complications require immediate medical attention.

Call 911 or go to the nearest emergency room for:

• Psychiatric Crises: Suicidal thoughts, plans of self-harm, or severe aggression/agitation that puts the patient or caregivers in immediate physical danger. Contact crisis services immediately.
• Choking or Aspiration: If a person is unable to clear their airway while eating or drinking, or if they experience sudden, severe difficulty breathing ^[6][7].
• Signs of Aspiration Pneumonia or Infection: Sudden fever, shortness of breath, chest pain, persistent severe cough, or acute dehydration (reduced urine) after suspected choking ^[7].
• New or Prolonged Seizures: While unusual, some people with HDL1 develop epilepsy ^[2]. Seek emergency care for a first-time seizure, a seizure lasting longer than five minutes, or repeated seizures without waking up in between ^[8].
• Severe Head Injury: Any major fall resulting in a head impact, loss of consciousness, or sudden acute neurologic change.
• Sudden Safety Risks: A sudden, severe state of confusion that puts the person or their caregivers at risk of injury.

Contact your specialist promptly (within 24-48 hours) for:

• Dysphagia: If you notice frequent coughing, gagging, or a “wet” gurgly voice during or after meals. This can indicate dysphagia (swallowing difficulty), which increases the risk of aspiration pneumonia (a lung infection caused by food or liquid entering the lungs) ^[6][7].
• New or Worsening Psychiatric Symptoms: Worsening depression, new hallucinations, or escalating irritability that isn’t immediately dangerous but is distressing.
• Frequent Falls: A sudden increase in falls or a “near-miss” that suggests a change in balance or coordination ^[9].