PMID- 31655616 OWN - NLM STAT- MEDLINE DCOM- 20200706 LR - 20200706 IS - 1750-1172 (Electronic) IS - 1750-1172 (Linking) VI - 14 IP - 1 DP - 2019 Oct 26 TI - Neutral lipid storage disease with myopathy in China: a large multicentric cohort study. PG - 234 LID - 10.1186/s13023-019-1209-z [doi] LID - 234 AB - BACKGROUND: Neutral lipid storage disease with myopathy (NLSDM) is a rare clinical heterogeneous disorder caused by mutations in the patatin-like phospholipase domain-containing 2 (PNPLA2) gene. NLSDM usually presents skeletal myopathy, cardiomyopathy and the multiple organs dysfunction. Around 50 cases of NLSDM have been described worldwide, whereas the comprehensive understanding of this disease are still limited. We therefore recruit NLSDM patients from 10 centers across China, summarize the clinical, muscle imaging, pathological and genetic features, and analyze the genotype-phenotype relationship. RESULTS: A total of 45 NLSDM patients (18 men and 27 women) were recruited from 40 unrelated families. Thirteen patients were born from consanguineous parents. The phenotypes were classified as asymptomatic hyperCKemia (2/45), pure skeletal myopathy (18/45), pure cardiomyopathy (4/45), and the combination of skeletal myopathy and cardiomyopathy (21/45). Right upper limb weakness was the early and prominent feature in 61.5% of patients. On muscle MRI, the long head of the biceps femoris, semimembranosus and adductor magnus on thighs, the soleus and medial head of the gastrocnemius on lower legs showed the most severe fatty infiltration. Thirty-three families were carrying homozygous mutations, while seven families were carrying compound heterozygous mutations. A total of 23 mutations were identified including 11 (47.8%) point mutations, eight (34.8%) deletions and four (17.4%) insertions. c.757 + 1G > T, c.245G > A and c.187 + 1G > A were the three most frequent mutations. Among four groups of phenotypes, significant differences were shown in disease onset (< 20 years versus >/=20 years old, p = 0.003) and muscle pathology (with rimmed vacuoles versus without rimmed vacuoles, p = 0.001). PNPLA2 mutational type or functional defects did not show great impact on phenotypes. CONCLUSION: We outline the clinical and genetic spectrum in a large cohort of NLSDM patients. Selective muscle fatty infiltration on posterior compartment of legs are characteristic of NLSDM. Chinese patients present with distinctive and relative hotspot PNPLA2 mutations. The disease onset age and pathological appearance of rimmed vacuoles are proved to be related with the clinical manifestations. The phenotypes are not strongly influenced by genetic defects, suggesting the multiple environmental risk factors in the development of NLSDM. FAU - Zhang, Wei AU - Zhang W AD - Department of Neurology, Peking University First Hospital, No.8 Xishiku Street, West District, Beijing, 100034, China. FAU - Wen, Bing AU - Wen B AD - Department of Neurology, Qilu Hospital of Shandong University, No. 107, West Wenhua Road, Jinan, 250012, Shandong, China. FAU - Lu, Jun AU - Lu J AD - Department of Neurology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China. FAU - Zhao, Yawen AU - Zhao Y AD - Department of Neurology, Peking University First Hospital, No.8 Xishiku Street, West District, Beijing, 100034, China. FAU - Hong, Daojun AU - Hong D AD - Department of Neurology, Peking University People's Hospital, Beijing, People's Republic of China. FAU - Zhao, Zhe AU - Zhao Z AD - Department of Neurology, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei province, People's Republic of China. FAU - Zhang, Cheng AU - Zhang C AD - Department of Neurology, the First Affiliated Hospital of Sun yat-sen University, Guangzhou, Guangdong province, People's Republic of China. FAU - Luo, Yuebei AU - Luo Y AD - Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan province, People's Republic of China. FAU - Qi, Xueliang AU - Qi X AD - Department of Neurology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi province, People's Republic of China. FAU - Zhang, Yingshuang AU - Zhang Y AD - Department of Neurology, Third Hospital, Peking University, Beijing, People's Republic of China. FAU - Song, Xueqin AU - Song X AD - Department of Neurology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei province, People's Republic of China. FAU - Zhao, Yuying AU - Zhao Y AD - Department of Neurology, Qilu Hospital of Shandong University, No. 107, West Wenhua Road, Jinan, 250012, Shandong, China. FAU - Zhao, Chongbo AU - Zhao C AD - Department of Neurology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China. FAU - Hu, Jing AU - Hu J AD - Department of Neurology, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei province, People's Republic of China. FAU - Yang, Huan AU - Yang H AD - Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan province, People's Republic of China. FAU - Wang, Zhaoxia AU - Wang Z AD - Department of Neurology, Peking University First Hospital, No.8 Xishiku Street, West District, Beijing, 100034, China. FAU - Yan, Chuanzhu AU - Yan C AD - Department of Neurology, Qilu Hospital of Shandong University, No. 107, West Wenhua Road, Jinan, 250012, Shandong, China. chuanzhuyan@163.com. FAU - Yuan, Yun AU - Yuan Y AUID- ORCID: 0000-0003-3282-9123 AD - Department of Neurology, Peking University First Hospital, No.8 Xishiku Street, West District, Beijing, 100034, China. yuanyun2002@126.com. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20191026 PL - England TA - Orphanet J Rare Dis JT - Orphanet journal of rare diseases JID - 101266602 RN - Neutral Lipid Storage Disease with Myopathy SB - IM MH - China MH - Cohort Studies MH - Female MH - Genetic Predisposition to Disease MH - Humans MH - Lipid Metabolism, Inborn Errors/*diagnostic imaging/*epidemiology/genetics MH - Male MH - Muscle, Skeletal/diagnostic imaging MH - Muscular Diseases/*diagnostic imaging/*epidemiology/genetics PMC - PMC6815004 OTO - NOTNLM OT - Cardiomyopathy OT - Neutral lipid storage disease with myopathy OT - Patatin-like phospholipase domain-containing 2 OT - Rimmed vacuole OT - Skeletal myopathy COIS- The authors declare no conflicts of interest. EDAT- 2019/10/28 06:00 MHDA- 2020/07/07 06:00 PMCR- 2019/10/26 CRDT- 2019/10/28 06:00 PHST- 2019/04/14 00:00 [received] PHST- 2019/09/24 00:00 [accepted] PHST- 2019/10/28 06:00 [entrez] PHST- 2019/10/28 06:00 [pubmed] PHST- 2020/07/07 06:00 [medline] PHST- 2019/10/26 00:00 [pmc-release] AID - 10.1186/s13023-019-1209-z [pii] AID - 1209 [pii] AID - 10.1186/s13023-019-1209-z [doi] PST - epublish SO - Orphanet J Rare Dis. 2019 Oct 26;14(1):234. doi: 10.1186/s13023-019-1209-z.