Huntington’s Disease (HD) and Amyotrophic Lateral Sclerosis (ALS), commonly known as Lou Gehrig’s Disease, are often confused because both are progressive neurological disorders leading to physical decline. While both affect the nervous system and motor function, they are distinct diseases with different underlying causes and primary symptom profiles. Understanding their unique biological mechanisms and clinical manifestations shows why they are not the same.
The Defining Characteristics of Huntington’s Disease
Huntington’s Disease is a hereditary neurodegenerative disorder caused by a single, known genetic mutation in the HTT gene located on chromosome 4. This mutation is an expansion of a cytosine-adenine-guanine (CAG) trinucleotide repeat, which results in the production of an abnormally long and toxic huntingtin protein. Because this genetic defect is inherited in an autosomal dominant pattern, a person only needs to inherit one copy of the faulty gene to develop the disease.
The toxic protein causes nerve cells in the brain to decay over time, primarily affecting the basal ganglia and the cerebral cortex. This widespread damage leads to a triad of progressive symptoms: motor, cognitive, and psychiatric. The most recognized motor symptom is chorea, which presents as involuntary, jerky movements of the face, limbs, and trunk.
Cognitive abilities decline, leading to difficulties with reasoning, judgment, memory, and planning. Psychiatric symptoms, such as irritability, depression, anxiety, and mood swings, often appear early in the disease course, sometimes years before physical symptoms manifest. The disease progressively worsens over 10 to 25 years, eventually leading to a loss of the ability to walk, talk, and reason.
The Defining Characteristics of Lou Gehrig’s Disease (ALS)
Lou Gehrig’s Disease (ALS) is a progressive neurological disorder characterized by the selective death of motor neurons. These nerve cells in the brain and spinal cord control voluntary muscle movement, sending messages to the muscles to initiate action. As these cells degenerate and die, they can no longer transmit signals, causing the muscles to weaken, twitch, and waste away (atrophy).
The primary manifestation of ALS is progressive muscle weakness and paralysis, which can begin in the limbs (limb-onset) or with difficulty speaking and swallowing (bulbar-onset). This weakness advances to affect the ability to walk, use the arms, and eventually breathe as respiratory muscles fail. In contrast to HD, the senses and mental functioning are often spared for the majority of the disease course.
The cause of ALS is largely sporadic, meaning it occurs randomly with no known family history in about 90% of cases. The remaining cases are familial, involving various genetic mutations. The focus of the disease is strictly on the motor system, leading to hyperreflexia and spasticity from upper motor neuron damage, and muscle fasciculations and atrophy from lower motor neuron damage.
Why They Are Not the Same Condition
Huntington’s Disease and Lou Gehrig’s Disease are fundamentally different conditions, distinguishable by their etiology, affected systems, and hallmark symptoms. The cause of HD is a single, dominant genetic defect in the HTT gene, ensuring anyone who inherits it will develop the disease. ALS, conversely, is largely a sporadic disease, with the cause remaining unknown in most patients.
The diseases target different structures: HD causes widespread damage to the brain, particularly the basal ganglia and cerebral cortex, which control coordination, cognition, and mood. ALS is a motor neuron disease that specifically destroys the nerve cells responsible for voluntary muscle control. This difference results in contrasting hallmark symptoms. The defining motor feature of HD is chorea (involuntary, dance-like movements), coupled with early cognitive decline and psychiatric symptoms. The defining feature of ALS is muscle weakness and atrophy, which progresses to total paralysis.