Machado-Joseph disease versus hereditary spastic paraplegia: case report

Area of Science:

• Neurogenetics
• Neurology
• Clinical Genetics

Background:

• Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is the most prevalent autosomal dominant spinocerebellar ataxia.
• MJD is characterized by significant phenotypic variability, making diagnosis challenging.
• Recent studies have identified MJD presenting with spastic paraparesis in Japanese populations.

Observation:

• A 41-year-old woman presented with a clinical phenotype consistent with complicated hereditary spastic paraplegia (HSP).
• Her father had a history of an undiagnosed progressive neurological disorder with parkinsonian features.
• Genetic analysis revealed an expanded allele with 66 CAG repeats and a normal allele with 22 repeats in the ATXN3 gene, confirming MJD.

Findings:

• The patient's presentation with complicated hereditary spastic paraplegia (HSP) is an atypical but recognized phenotype of Machado-Joseph disease (MJD).
• The presence of a family history with diverse neurodegenerative features (parkinsonism) further supports MJD in the differential diagnosis.
• The genetic confirmation of an expanded CAG repeat in the ATXN3 gene definitively diagnosed MJD.

Implications:

• Machado-Joseph disease (MJD) should be included in the differential diagnosis for autosomal dominant complicated hereditary spastic paraplegia (HSP).
• A high index of suspicion for MJD is warranted in patients with HSP and family members exhibiting varied neurodegenerative conditions.
• Recognizing the phenotypic variability of MJD is crucial for accurate and timely diagnosis, potentially improving patient management and genetic counseling.