**5.4 Other metabolic or complex autosomal recessive disorders that have ataxia as an associated feature**

### *5.4.1 Niemann-pick disease type C*

Niemann-Pick disease (PC) is caused by autosomal recessive mutations in either the NPC1 or NPC2 gene. NP1 encodes a transmembrane protein and NP2 an intralysosomal protein, the deficiency of which results in the intracellular accumulation of cholesterol and complex lipids, such as sphingolipids and phospholipids, within the endosomal/ lysosomal system [74]. NPC has a heterogeneous spectrum of signs and symptoms in visceral, neurologic, and psychiatric domains, with characteristic symptomatology depending on the age of onset. Ataxia is a frequent manifestation in late infantile, juvenile and adult forms and can be associated with vertical gaze palsy, epilepsy, dystonia and cataplexy [75]. The prognosis is correlated with the age at onset of the neurological manifestations, with early-onset forms progressing more rapidly than late-onset forms [74]. MRI and CT may be normal or show cerebellar or cortical atrophy [76].

### *5.4.2 Wilson disease (WD)*

Wilson Disease (WD) is caused by mutations in the ATP7B gene, which encodes the synthesis of an ATPase that participates in the copper transport, located preferentially in the liver but also in the brain [77]. WD generally presents in childhood and young adulthood. The most common age of presentation is 10 to 20 years [78]. WD have different forms of presentation, including fulminant hepatitis, psychosis, or neurological disorder (tremor, dystonia, akinetic-rigid syndrome, and ataxia). A characteristic ophthalmological manifestation includes the Kayser-Fleischer ring [79]. MRI imaging findings are variable, with neurological patients classically presenting with bilateral high signal intensities on T2 and Flair-weighted images in the basal ganglia, the mesencephalon and the cerebellum [77]. Low levels of ceruloplasmin and copper are detected in the blood, the excretion of which is increased in urine [78]. D-penicillamine and trientine as chelators, and tetrathiomolybdate and zinc sulfate are the usual treatment [79].
