What differentiates Huntington's chorea from Lubag (X-linked dystonia-parkinsonism)?

From the Guidelines

Huntington's chorea and Lubag (X-linked dystonia-parkinsonism) can be differentiated based on their distinct genetic basis, inheritance patterns, and clinical presentation, with Huntington's chorea being caused by an autosomal dominant mutation in the HTT gene and Lubag being caused by mutations in the TAF1 gene on the X chromosome. The key differences between the two conditions lie in their genetic origins, affected populations, and symptom progression. Huntington's chorea is characterized by an expanded CAG repeat sequence in the HTT gene on chromosome 4, affecting men and women equally, and typically presents with chorea, cognitive decline, and psychiatric symptoms in middle age (30s-50s) 1. In contrast, Lubag is caused by mutations in the TAF1 gene on the X chromosome, predominantly affecting men of Filipino descent, particularly those from Panay Island, and initially presents with focal dystonia that generalizes over time, followed by parkinsonian features like bradykinesia and rigidity.

Some of the key features that distinguish Huntington's chorea from Lubag include:

• Genetic basis: Huntington's chorea is caused by an autosomal dominant mutation in the HTT gene, while Lubag is caused by mutations in the TAF1 gene on the X chromosome.
• Inheritance pattern: Huntington's chorea affects men and women equally, while Lubag predominantly affects men of Filipino descent.
• Clinical presentation: Huntington's chorea typically presents with chorea, cognitive decline, and psychiatric symptoms, while Lubag initially presents with focal dystonia that generalizes over time, followed by parkinsonian features.
• Age of onset: Both conditions typically have an age of onset between 35-45 years, but Lubag progresses more rapidly than Huntington's, often leading to severe disability within 10-15 years.

The management of these conditions also differs based on symptom presentation, with Huntington's often requiring medications like tetrabenazine for chorea and antipsychotics for behavioral symptoms, while Lubag may respond to anticholinergics, botulinum toxin injections for dystonia, and levodopa for parkinsonian features 1. It is essential to note that while both conditions lack curative treatments, accurate diagnosis and management can significantly impact the quality of life for affected individuals. According to the most recent guidelines, genetic testing to determine the CAG repeat number for each allele is commercially available and the diagnostic test of choice for Huntington's chorea 1.

From the Research

Differentiation between Huntington's Chorea and Lubag (X-linked Dystonia-Parkinsonism)

• Clinical Presentation: Huntington's chorea is characterized by progressive chorea, cognitive decline, and psychiatric symptoms 2. In contrast, Lubag (X-linked dystonia-parkinsonism) presents with a wide spectrum of movement disorders, including dystonia, tremor, parkinsonism, myoclonus, chorea, and myorhythmia 2.
• Genetic Factors: Huntington's chorea is an autosomal dominant disorder, whereas Lubag is an X-linked recessive disorder, primarily affecting Filipino men with maternal roots from the Philippine island of Panay 3, 4.
• Neuropathology: The major neuropathology of Lubag is progressive neuronal loss in the neostriatum (i.e., the caudate nucleus and putamen) 4, 5. In contrast, Huntington's chorea is characterized by atrophy of the caudate nucleus and putamen, with a distinct pattern of neuronal loss and astrocytosis.
• Demographic Characteristics: Lubag is endemic to the Philippine island of Panay and primarily affects Filipino men 2, 3. Huntington's chorea, on the other hand, has a worldwide distribution and affects both men and women.
• Symptom Progression: Lubag is characterized by a progressive course, with dystonia often preceding parkinsonism 4. In contrast, Huntington's chorea typically presents with a combination of chorea, cognitive decline, and psychiatric symptoms, with a gradual progression of symptoms over time.
• Response to Treatment: Patients with Lubag may respond to treatment with carbidopa/levodopa, particularly those with parkinsonism 6. In contrast, Huntington's chorea is generally refractory to treatment, although symptomatic therapies may be used to manage chorea and other symptoms.