Hereditary neurodegenerative diseases represent a heterogeneous group of genetic disorders characterized by progressive involvement of the central and/or peripheral nervous system, often manifesting with ataxia, spasticity, dystonia, and neuropathy. This chapter provides a comprehensive overview of major autosomal recessive cerebellar ataxias (ARCAs), including Friedreich’s ataxia (FRDA), ataxia telangiectasia (AT), ataxia with oculomotor apraxia types 1 and 2, and Charlevoix–Saguenay spastic ataxia (ARSACS), cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS), X-linked Charcot–Marie–Tooth disease (CMTX), dopa-responsive dystonias (DRD), episodic ataxias, fragile X–associated tremor/ataxia syndrome (FXTAS), hereditary spastic paraplegias (HSP), nonmetabolic inherited leukodystrophies and leukoencephalopathies, spinal muscular atrophy (SMA), or spinocerebellar ataxias (SCA). Each disease is reviewed in terms of genetic basis, clinical phenotype, imaging patterns, blood and cerebrospinal fluid markers, and electrophysiological findings. Emphasis is placed on overlapping clinical features with multiple sclerosis (MS) and other acquired inflammatory demyelinating diseases, which can lead to misdiagnosis and inappropriate immunotherapy. The importance of neuroimaging red flags, atypical cerebrospinal fluid (CSF) profiles, and genetic testing is underscored. Many of these conditions lack curative treatments but benefit from early recognition and supportive care. The chapter provides a practical diagnostic approach and differential framework for neurologists to distinguish inherited neurodegenerative ataxias and paraplegias from acquired demyelinating diseases.