Abstract
RATIONALE: Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, a rare autosomal dominant neurodegenerative disorder caused by cytosine-adenine-guanine repeat expansions in ATXN3, lacks effective therapies. This case report highlights the clinical and genetic features of a family with 5 affected members to emphasize the challenges in diagnosis, management, and the need for targeted therapies. PATIENT CONCERNS: A 33-year-old male proband presented with progressive gait instability, limb incoordination, and dysarthria for more than 2 years. The symptoms worsened in cold weather and were accompanied by head swelling and muscle weakness. The patient reported a strong family history of similar neurological symptoms across the 3 generations. DIAGNOSIS: Clinical evaluation revealed cerebellar ataxia, a wide-based gait, and impaired coordination. Brain MRI revealed bilateral cerebellar atrophy. Genetic testing confirmed the presence of a pathogenic ATXN3 allele with 78 cytosine-adenine-guanine repeats (normal range: ≤49), which is consistent with SCA3. Familial genetic analysis identified identical mutations in 4 additional relatives. INTERVENTIONS: Supportive treatment included improvement in circulation, neuroprotective agents, and symptomatic management. No disease-modifying therapies were administered, owing to their limited availability. OUTCOMES: The patient's condition did not improve during hospitalization, reflecting the progressive nature of the SCA3. Similar outcomes were observed in affected family members. LESSONS: Early genetic testing is critical for a definitive diagnosis, especially in familial cases. The lack of effective therapies underscores the urgency of clinical trials that target polyglutamine toxicity. Multidisciplinary care and patient education are essential for the management of this debilitating disease.