**1.3. Clinical presentation and symptoms of Niemann-Pick disease**

Systemic involvement of liver, spleen, or lung, is present in ≥85% of patients, and precedes the development of neurologic symptoms. The age of onset and clinical presentation of NPD-C is highly variable.

*Neonatal and infantile presentations*: Occasionally, ultrasound examination in late pregnancy has detected fetal ascites; infants thus identified typically have a severe neonatal liver disease with jaundice and persistent ascites. Infiltration of the lungs with foam cells can be present. Many infants die at this stage. Of children who survive, many have hypotonia and psychomotor retardation whereas others may have complete resolution of symptoms, only to present with neurologic disease many years later [4].

*Childhood presentations*: These patients typically have cerebellar involvement characterized by clumsiness and gait problems progressing to frank ataxia and slow cognitive deterioration Vertical supranuclear ophthalmoplegia is another early manifestation. Progressive dystonia, dysarthria, and dysphagia occur, eventually impairing oral feeding, and approximately onethird of patients develop seizures [4].

*Adolescent and adult presentations*: The clinical presentation is similar to childhood onset with ataxia, supranuclear vertical gaze palsy, cognitive impairment, except that progression is generally much slower. Other adults present with cognitive dysfunction or psychiatric disturbances as major depression, schizophrenia, or bipolar disorder [4].
