Three cases of juvenile and adult-onset Niemann-Pick disease type C: Variability in neurological and psychiatrical phenotypes (P1.149)

Objective: To illustrate clinical variability of juvenile and adult-onset Niemann-Pick disease type C (NPC). Background: NPC is a lysosomal storage disorder, which could be treated by substrate reduction therapy using miglustat, a reversible inhibitor of glucosylceramide synthase. In order to prevent severe neurological complications, it is important to diagnose NPC at an early stage. However, such diagnosis is challenging due to extensive clinical variability: most cases are diagnosed long after the onset of neurological symptoms. Here, we present three cases of NPC including one which could successfully be diagnosed at an early stage clinically masquerading as schizophrenia. Design/Methods: Case report. Results: Case 1: A 25-year-old man presented with a 14-year history of mental retardation, gait disturbance, delusions, frequent falls and dysphagia. Neurological examination revealed vertical supranuclear gaze palsy and involuntary movements (choreoathetosis, dystonia, and myoclonus). Filipin staining in cultured skin fibroblasts showed classical pattern. NPC1 gene analysis detected compound heterozygous mutations including a known missense mutation c.1421C>T (p.P474L) and a novel missense mutation c.3722T>C (p.L1241S). Overall, the diagnosis of juvenile-onset NPC was made. Case 2 and 3: A 28-year-old woman presented with a 1-year history of orofacial dystonia (case 2). Her elderly sister, a 35-year-old woman, had a 13-years history of schizophrenia (case 3). Apart from dystonia or schizophrenia, both of them were neurologically intact. Ultrasonography detected mild splenomegaly in both cases (infantile marked splenomegaly was noted in case 2). In both cases, filipin staining in cultured skin fibroblasts showed variant pattern. NPC1 gene analysis revealed compound heterozygous mutations including a known missense mutation c.3011C>T (p.S1004L) and a novel frameshift mutation c.160_161insG (p.D54GfsX4). Above all, the diagnosis of adult-onset NPC was made. Conclusions: Remarkable clinical variability was observed in our cases, including a case clinically indistinguishable from schizophrenia. Establishing accurate diagnosis in NPC patients presenting with psychiatric symptoms should be imperative to initiate disease-specific therapies. Disclosure: Dr. Kawazoe has nothing to disclose. Dr. Yamamoto has nothing to disclose. Dr. Narita has nothing to disclose. Dr. Ohno has nothing to disclose. Dr. Nanba has nothing to disclose. Dr. Noguchi has nothing to disclose. Dr. Takahashi has nothing to disclose. Dr. Ogawa has nothing to disclose. Dr. Murata has received research support from AbbVie. Dr. Takahashi has nothing to disclose.