Niemann-Pick disease type C1 predominantly involving the frontotemporal region, with cortical and brainstem Lewy bodies

An autopsy case

Yoichi Chiba, Hiraku Komori, Shiro Takei, Sanae Ishii, Noriko Kawamura, Kaori Adachi, Eiji Nanba, Masanori Hosokawa, Yasushi Enokido, Zen Kouchi, Futoshi Yoshida, Atsuyoshi Shimada

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage disorder. Two disease-causing genes (NPC1 and NPC2) have been identified. NPC is characterized by neuronal and glial lipid storage and NFTs. Here, we report a man with juvenile-onset progressive neurological deficits, including pyramidal signs, ataxia, bulbar palsy, vertical supranuclear ophthalmoplegia, and psychiatric symptoms; death occurred at age 37 before definitive clinical diagnosis. Post mortem gross examination revealed a unique distribution of brain atrophy, predominantly in the frontal and temporal lobes. Microscopically, lipid storage in neurons and widely distributed NFTs were observed. Lipid storage cells appeared in systemic organs and filipin staining indicated intracellular cholesterol accumulation in hepatic macrophages. Electron microscopy revealed accumulation of lipids and characteristic oligolamellar inclusions. These findings suggested an NPC diagnosis. Neuronal loss and gliosis were frequently accompanied by NFTs and occurred in the frontal and temporal cortices, hippocampus, amygdala, basal forebrain, basal ganglia, thalamus, substantia nigra and brain stem nuclei. Lewy bodies (LBs) were observed in most, but not all, regions where NFTs were evident. In contrast, neuronal lipid storage occurred in more widespread areas, including the parietal and occipital cortices where neurodegeneration with either NFTs or LBs was minimal. Molecular genetic analysis demonstrated that the patient had compound heterozygous mutations in the cysteine-rich loop (A1017T and Y1088C) of the NPC1 gene. To our knowledge there has been no previous report of the A1017T mutation. The pathological features of this patient support the notion that NPC has an aspect of α-synucleinopathy, and long-term survivors of NPC may develop a frontotemporal-predominant distribution of brain atrophy.

Original languageEnglish (US)
Pages (from-to)49-57
Number of pages9
JournalNeuropathology
Volume34
Issue number1
DOIs
StatePublished - Feb 1 2014

Fingerprint

Type C Niemann-Pick Disease
Lewy Bodies
Brain Stem
Autopsy
Lipids
Frontal Lobe
Temporal Lobe
Atrophy
Progressive Bulbar Palsy
Filipin
Ophthalmoplegia
Occipital Lobe
Parietal Lobe
Mutation
Gliosis
Brain
Substantia Nigra
Ataxia
Amygdala
Basal Ganglia

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Chiba, Yoichi ; Komori, Hiraku ; Takei, Shiro ; Ishii, Sanae ; Kawamura, Noriko ; Adachi, Kaori ; Nanba, Eiji ; Hosokawa, Masanori ; Enokido, Yasushi ; Kouchi, Zen ; Yoshida, Futoshi ; Shimada, Atsuyoshi. / Niemann-Pick disease type C1 predominantly involving the frontotemporal region, with cortical and brainstem Lewy bodies : An autopsy case. In: Neuropathology. 2014 ; Vol. 34, No. 1. pp. 49-57.
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abstract = "Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage disorder. Two disease-causing genes (NPC1 and NPC2) have been identified. NPC is characterized by neuronal and glial lipid storage and NFTs. Here, we report a man with juvenile-onset progressive neurological deficits, including pyramidal signs, ataxia, bulbar palsy, vertical supranuclear ophthalmoplegia, and psychiatric symptoms; death occurred at age 37 before definitive clinical diagnosis. Post mortem gross examination revealed a unique distribution of brain atrophy, predominantly in the frontal and temporal lobes. Microscopically, lipid storage in neurons and widely distributed NFTs were observed. Lipid storage cells appeared in systemic organs and filipin staining indicated intracellular cholesterol accumulation in hepatic macrophages. Electron microscopy revealed accumulation of lipids and characteristic oligolamellar inclusions. These findings suggested an NPC diagnosis. Neuronal loss and gliosis were frequently accompanied by NFTs and occurred in the frontal and temporal cortices, hippocampus, amygdala, basal forebrain, basal ganglia, thalamus, substantia nigra and brain stem nuclei. Lewy bodies (LBs) were observed in most, but not all, regions where NFTs were evident. In contrast, neuronal lipid storage occurred in more widespread areas, including the parietal and occipital cortices where neurodegeneration with either NFTs or LBs was minimal. Molecular genetic analysis demonstrated that the patient had compound heterozygous mutations in the cysteine-rich loop (A1017T and Y1088C) of the NPC1 gene. To our knowledge there has been no previous report of the A1017T mutation. The pathological features of this patient support the notion that NPC has an aspect of α-synucleinopathy, and long-term survivors of NPC may develop a frontotemporal-predominant distribution of brain atrophy.",
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Chiba, Y, Komori, H, Takei, S, Ishii, S, Kawamura, N, Adachi, K, Nanba, E, Hosokawa, M, Enokido, Y, Kouchi, Z, Yoshida, F & Shimada, A 2014, 'Niemann-Pick disease type C1 predominantly involving the frontotemporal region, with cortical and brainstem Lewy bodies: An autopsy case', Neuropathology, vol. 34, no. 1, pp. 49-57. https://doi.org/10.1111/neup.12047

Niemann-Pick disease type C1 predominantly involving the frontotemporal region, with cortical and brainstem Lewy bodies : An autopsy case. / Chiba, Yoichi; Komori, Hiraku; Takei, Shiro; Ishii, Sanae; Kawamura, Noriko; Adachi, Kaori; Nanba, Eiji; Hosokawa, Masanori; Enokido, Yasushi; Kouchi, Zen; Yoshida, Futoshi; Shimada, Atsuyoshi.

In: Neuropathology, Vol. 34, No. 1, 01.02.2014, p. 49-57.

Research output: Contribution to journalArticle

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T1 - Niemann-Pick disease type C1 predominantly involving the frontotemporal region, with cortical and brainstem Lewy bodies

T2 - An autopsy case

AU - Chiba, Yoichi

AU - Komori, Hiraku

AU - Takei, Shiro

AU - Ishii, Sanae

AU - Kawamura, Noriko

AU - Adachi, Kaori

AU - Nanba, Eiji

AU - Hosokawa, Masanori

AU - Enokido, Yasushi

AU - Kouchi, Zen

AU - Yoshida, Futoshi

AU - Shimada, Atsuyoshi

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage disorder. Two disease-causing genes (NPC1 and NPC2) have been identified. NPC is characterized by neuronal and glial lipid storage and NFTs. Here, we report a man with juvenile-onset progressive neurological deficits, including pyramidal signs, ataxia, bulbar palsy, vertical supranuclear ophthalmoplegia, and psychiatric symptoms; death occurred at age 37 before definitive clinical diagnosis. Post mortem gross examination revealed a unique distribution of brain atrophy, predominantly in the frontal and temporal lobes. Microscopically, lipid storage in neurons and widely distributed NFTs were observed. Lipid storage cells appeared in systemic organs and filipin staining indicated intracellular cholesterol accumulation in hepatic macrophages. Electron microscopy revealed accumulation of lipids and characteristic oligolamellar inclusions. These findings suggested an NPC diagnosis. Neuronal loss and gliosis were frequently accompanied by NFTs and occurred in the frontal and temporal cortices, hippocampus, amygdala, basal forebrain, basal ganglia, thalamus, substantia nigra and brain stem nuclei. Lewy bodies (LBs) were observed in most, but not all, regions where NFTs were evident. In contrast, neuronal lipid storage occurred in more widespread areas, including the parietal and occipital cortices where neurodegeneration with either NFTs or LBs was minimal. Molecular genetic analysis demonstrated that the patient had compound heterozygous mutations in the cysteine-rich loop (A1017T and Y1088C) of the NPC1 gene. To our knowledge there has been no previous report of the A1017T mutation. The pathological features of this patient support the notion that NPC has an aspect of α-synucleinopathy, and long-term survivors of NPC may develop a frontotemporal-predominant distribution of brain atrophy.

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