Familial Case Series of Neurodegenerative Disorders With Hematobiochemical Correlates: Insights From Four Related Patients

Neurodegenerative disorders, including spinocerebellar ataxias (SCAs) and hereditary spastic paraplegias (HSPs), are clinically heterogeneous conditions with frequent phenotypic overlap. Familial clusters offer vital opportunities to examine intrafamilial variability and systemic disease manifestations. In this case series, we evaluated four related patients from a single pedigree via neurological examination, hematobiochemical profiling, and neuroimaging. The index proband exhibited classical features of Spinocerebellar Ataxia Type 3 (SCA3) or Machado-Joseph disease (MJD), confirmed via molecular detection of a pathogenic ataxin-3 (ATXN3) gene mutation. Conversely, related family members demonstrated divergent phenotypes consistent with hereditary spastic paraplegia and sensory-motor peripheral neuropathy. Across the cohort, recurring hematological anomalies (including microcytic hypochromic anemia and neutrophilic leukocytosis) and prominent autonomic dysfunction (achalasia cardia and neurogenic urinary retention) were identified. These findings highlight the variable expressivity of familial neurodegeneration and underscore the importance of recognizing these conditions as systemic, multi-organ diseases requiring integrated, multidisciplinary management.