Familial spinocerebellar ataxia type 3: A case report of multi-generational presentation

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.

Keywords: MJD; SCA3; family; gene mutation; spinocerebellar ataxia type 3.

Figure 1.

Presents a pedigree chart of a family affected by SCA3, using standard symbols: circles for females, squares for males, filled shapes for individuals with SCA3, and open shapes for unaffected members. The proband (the first diagnosed case in the family) is typically marked with an arrow or highlighted symbol. Diagonal lines denote deceased individuals. This chart visually summarizes the distribution of the condition within the family lineage. SCA3 = spinocerebellar ataxia type 3.

Figure 2.

(A and B) Head MRI results of the proband: the brain parenchyma shows no abnormal signals, with a clear demarcation between the gray and white matter. The size and signal of the ventricular system were normal. There was bilateral widening of the cerebellar sulci, whereas the cerebral sulci and cisterns appeared normal. The midline structures were not displaced, and the brainstem contour was well defined. MRI = magnetic resonance imaging.