PMID- 30738494
OWN - NLM
STAT- MEDLINE
DCOM- 20200102
LR  - 20231213
IS  - 0722-5091 (Print)
IS  - 0722-5091 (Linking)
VI  - 38
IP  - 4
DP  - 2019 Jul/Aug
TI  - Clinical findings and autophagic pathology in neutral lipid storage disease with 
      myopathy.
PG  - 157-167
LID - 10.5414/NP301159 [doi]
AB  - Neutral lipid storage disease with myopathy (NLSDM) is a triglyceride metabolic 
      disorder caused by defects of adipose triglyceride lipases (ATGL). The 
      coexistence of lipid vacuoles and rimmed vacuoles in the myofibers is a 
      characteristic pathological change in some NLSDM cases. However, it has not been 
      explored whether autophagic abnormalities exist in the NLSDM myofibers with 
      rimmed vacuole. Herein, we report that 5 patients with NLSDM initially presented 
      with muscle weakness in the right arm related to long-term physical efforts, then 
      developed muscle weakness of other limbs. Pathogenic mutations in the PNPLA2 gene 
      were identified in all patients. Myopathological analysis showed a coexistence of 
      massive lipid vacuoles and rimmed vacuoles, which was not associated with the age 
      of onset or mutation sites, but closely related to the severity of muscle 
      degeneration. The rimmed vacuoles showed strong immunopositivity to autophagic 
      markers, but were negative to apoptotic markers. Significant immunoreactivity of 
      p62 was observed in the rimmed vacuoles, while the lysosomal marker LAMP1 was 
      severely decreased. Our study expanded the clinical and genetic spectrum of 
      NLSDM. Loss of ATGL activity in muscle fibers with rimmed vacuoles induced a 
      marked increase in autophagic formation, but lowered down the turnover of 
      autolysosomes due to malfunction of lysosomes.
FAU - Hong, Daojun
AU  - Hong D
FAU - Zheng, Junjun
AU  - Zheng J
FAU - Xin, Ling
AU  - Xin L
FAU - Xiang, Yining
AU  - Xiang Y
FAU - Luan, Xinghua
AU  - Luan X
FAU - Cao, Li
AU  - Cao L
FAU - Cong, Lu
AU  - Cong L
FAU - Fang, Pu
AU  - Fang P
FAU - Zhang, Jun
AU  - Zhang J
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Clin Neuropathol
JT  - Clinical neuropathology
JID - 8214420
RN  - 0 (LAMP1 protein, human)
RN  - 0 (Lysosomal Membrane Proteins)
RN  - EC 3.1.1.3 (Lipase)
RN  - EC 3.1.1.3 (PNPLA2 protein, human)
RN  - Chanarin-Dorfman Syndrome
RN  - Neutral Lipid Storage Disease with Myopathy
SB  - IM
MH  - Adult
MH  - Apoptosis/physiology
MH  - Autophagy
MH  - Female
MH  - Humans
MH  - Ichthyosiform Erythroderma, Congenital/genetics
MH  - Lipase/*genetics
MH  - Lipid Metabolism, Inborn Errors/diagnosis/*genetics/pathology
MH  - Lysosomal Membrane Proteins/genetics
MH  - Male
MH  - Middle Aged
MH  - Muscle, Skeletal/*pathology
MH  - Muscular Diseases/diagnosis/genetics/*pathology
MH  - Mutation/genetics
MH  - Vacuoles/genetics
EDAT- 2019/02/11 06:00
MHDA- 2020/01/03 06:00
CRDT- 2019/02/11 06:00
PHST- 2019/06/27 00:00 [accepted]
PHST- 2019/02/11 06:00 [pubmed]
PHST- 2020/01/03 06:00 [medline]
PHST- 2019/02/11 06:00 [entrez]
AID - 18090 [pii]
AID - 10.5414/NP301159 [doi]
PST - ppublish
SO  - Clin Neuropathol. 2019 Jul/Aug;38(4):157-167. doi: 10.5414/NP301159.