TY - JOUR
T1 - Phenotypic variability of Niemann-Pick disease type C including a case with clinically pure schizophrenia
T2 - A case report
AU - Kawazoe, Tomoya
AU - Yamamoto, Toshiyuki
AU - Narita, Aya
AU - Ohno, Kousaku
AU - Adachi, Kaori
AU - Nanba, Eiji
AU - Noguchi, Atsuko
AU - Takahashi, Tsutomu
AU - Maekawa, Masamitsu
AU - Eto, Yoshikatsu
AU - Ogawa, Masafumi
AU - Murata, Miho
AU - Takahashi, Yuji
N1 - Funding Information:
This work was partially supported by Grants-in-Aid for Scientific Research (16 K20900) from the Japan Society for the Promotion of Science. Moreover, a part of this work was supported by a grant from the AMED - Project for Baby and Infant Research of Health and Development to Adolescent and Young adult, 2017–2018.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/8/17
Y1 - 2018/8/17
N2 - Background: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder with severe prognosis. Disease-specific therapy is crucial to prevent disease progression; however, diagnosing NPC is quite difficult because of remarkably variable clinical presentations. The NPC Suspicion Index (NPC-SI) was developed to overcome this problem. Identifying preclinical cases is important for prevention and therapy. Here, we report three newly diagnosed NPC cases, one typical juvenile-onset case and the cases of two sisters with symptoms neurologically/psychiatrically indistinguishable from dystonia and schizophrenia, respectively. Case presentation: In Case 1, a 25-year-old man presented with a 14-year history of intellectual disability, clumsiness, spastic ataxia, dysphagia, and frequent falls. Neurological examination revealed vertical supranuclear gaze palsy and involuntary movements. Ultrasonography revealed mild splenomegaly, and filipin staining of skin fibroblasts was positive with a variant staining pattern. NPC1 gene analysis showed compound heterozygous mutations, including c.1421C>T (p.P474L), a known causative mutation, and c.3722T>C (p.L1241S), a new mutation. In Case 2, a 28-year-old woman, the proband, who had marked splenomegaly in her childhood, survived well, contrary to the expected severe prognosis of infantile NPC. She had minor neuropsychiatric symptoms including auditory hallucinations, nocturnal urination, and sleep paralysis. At the age of 28years, she presented with a 1-year history of orofacial and oromandibular painful dystonia. The patient's 35-year-old sister (Case 3) was diagnosed with schizophrenia. In both cases, filipin staining of skin fibroblasts was positive with variant staining patterns, as well as elevated levels of urinary bile acids. NPC1 gene analysis showed compound heterozygous mutations including c.3011C>T (p.S1004L), a known causative mutation, and c.160_161insG (p.D54GfsX4), a new mutation. Their mother, who was under therapy with modafinil for narcolepsy, shared the latter mutation. Conclusions: Marked clinical variability was observed in our three cases. NPC could masquerade as a pure neuropsychiatric disorder such as dystonia or schizophrenia. Abdominal ultrasonography, history evaluation, and neurological examination were quite important in the diagnostic process.
AB - Background: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder with severe prognosis. Disease-specific therapy is crucial to prevent disease progression; however, diagnosing NPC is quite difficult because of remarkably variable clinical presentations. The NPC Suspicion Index (NPC-SI) was developed to overcome this problem. Identifying preclinical cases is important for prevention and therapy. Here, we report three newly diagnosed NPC cases, one typical juvenile-onset case and the cases of two sisters with symptoms neurologically/psychiatrically indistinguishable from dystonia and schizophrenia, respectively. Case presentation: In Case 1, a 25-year-old man presented with a 14-year history of intellectual disability, clumsiness, spastic ataxia, dysphagia, and frequent falls. Neurological examination revealed vertical supranuclear gaze palsy and involuntary movements. Ultrasonography revealed mild splenomegaly, and filipin staining of skin fibroblasts was positive with a variant staining pattern. NPC1 gene analysis showed compound heterozygous mutations, including c.1421C>T (p.P474L), a known causative mutation, and c.3722T>C (p.L1241S), a new mutation. In Case 2, a 28-year-old woman, the proband, who had marked splenomegaly in her childhood, survived well, contrary to the expected severe prognosis of infantile NPC. She had minor neuropsychiatric symptoms including auditory hallucinations, nocturnal urination, and sleep paralysis. At the age of 28years, she presented with a 1-year history of orofacial and oromandibular painful dystonia. The patient's 35-year-old sister (Case 3) was diagnosed with schizophrenia. In both cases, filipin staining of skin fibroblasts was positive with variant staining patterns, as well as elevated levels of urinary bile acids. NPC1 gene analysis showed compound heterozygous mutations including c.3011C>T (p.S1004L), a known causative mutation, and c.160_161insG (p.D54GfsX4), a new mutation. Their mother, who was under therapy with modafinil for narcolepsy, shared the latter mutation. Conclusions: Marked clinical variability was observed in our three cases. NPC could masquerade as a pure neuropsychiatric disorder such as dystonia or schizophrenia. Abdominal ultrasonography, history evaluation, and neurological examination were quite important in the diagnostic process.
KW - Dystonia
KW - Miglustat
KW - NPC1 mutation
KW - Niemann-Pick disease type C
KW - Schizophrenia
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U2 - 10.1186/s12883-018-1124-2
DO - 10.1186/s12883-018-1124-2
M3 - Article
C2 - 30119649
AN - SCOPUS:85051974833
VL - 18
JO - BMC Neurology
JF - BMC Neurology
SN - 1471-2377
IS - 1
M1 - 117
ER -