Neuropsychiatric presentation of Niemann-Pick type C disease: case report and literature review

Abstract

Introduction: Niemann-Pick type C (NP-C) is an inherited autosomal
recessive genetic disease, caused by mutations in the NPC1 and
NPC2 gene, causing neurovisceral lysosomal storage. Lysosomal
storage is consequence of cellular traffic defect that leads to glycos
phingolipid and cholesterol accumulation in many organs, progres
sing to premature cell death. This disease has a prevalence of 1:
120,000, in which about 95% of patients with the syndrome exhibit
alterations in the NPC1 gene and only 5% have mutations in NPC2
gene. Patients with NP-C disease may present several phenotypes,
from the neonatal-infantile form with visceral manifestations such
as organomegaly and cholestasis, to the juvenile-adult form, with
progressive neurological degeneration. Case report: 18-year-old fe
male patient referred for investigation of neuropsychiatric disorder
(“schizophrenia-like” and vertical supranuclear gaze palsy), associa
ted with motor manifestations (ataxia, mild dystonia and dysarthria).
According to the clinical findings and physical examination, Filipin
test and genetic sequencing were requested, confirming NP-C.
After diagnosis, patient was started on substrate reduction therapy
(TRS) with Miglustat, showing clinical stabilization. Discussion: NP-C
should be considered as a differential diagnosis of several diseases with
progressive visceral and neuropsychiatric manifestations, in order to direct
its investigation. Since NP-C is potentially treatable and given its progressive
character, early diagnosis becomes essential, not only for better clinical
prognosis of the patient, but also to allow family genetic counseling.