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Abstract Details

Identification of novel compound heterozygous mutation in Niemann-Pick disease type C gene
Movement Disorders
P14 - Poster Session 14 (11:45 AM-12:45 PM)

Niemann–Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disease with heterogenous neurological and systemic manifestations. The vast majority of cases (95%) are caused by mutations in the Niemann–Pick C1 protein (NPC1), whereas the reminder of cases are attributed to mutations in Niemann–Pick C2 protein (NPC2).  

To report a novel compound heterozygous mutation in two siblings with  Niemann-Pick disease type C who displayed distinct phenotypic presentation 
Case report

Case 1: A 57-year-old female presented with a 5-year history of progressive slowness, poor coordination, and cognitive decline. This was followed by generalized stiffness and recurrent ballistic movements within two years of onset.  Her poor postural stability lead to frequent falls. Initial neurological evaluation revealed severe dysarthric speech, moderate vertical eye movement limitation, spasticity and exaggerated deep tendon reflexes, along with dystonic movements. She progressed rapidly, developing generalized dystonia which made her bedbound.

Case 2: the young sibling of case 1, presented at the age of 56 with 8-year history of poor balance. Symptoms were slowly progressive, noted initially with changes in his balance, slurred speech, and poor coordination. He was also noticed to have mild cognitive changes. Examination revealed cerebellar dysarthria, with failure to generate saccades from primary position downwards. Deep tendon reflexes were brisk, with no evidence of muscle wasting, or spasticity. He showed signs of mild axial and appendicular ataxia.  The progression was slow, and he maintained his mobility without requiring walking aids.

Molecular genetic testing revealed compound heterozygous mutation in the NPC1 gene; c.180G>T (p.Gln60His) and c.3173C>A (p.Ala1058Asp).  All biochemical results were within normal range. Brain MRI showed generalized cerebral and cerebellar volume loss few years into the onset of symptoms in both patients.

Our report highlights the high intrafamilial heterogeneity and poor genotype-phenotype correlation in the case of Niemann–Pick disease type C. 
Ali Hussain Abusrair, MD (Qatif Health Network)
Dr. Abusrair has nothing to disclose.
Gabriel Amorelli, MD (University of Calgary) Dr. Amorelli has nothing to disclose.
Justyna Sarna, MD No disclosure on file