The abnormal storage of triglycerides (TG)  in skeletal muscle can be due to ETFDH mutations in the Riboflavin Responsive Multiple Acyl-CoA deficiency (RR-MADD), CPT2 mutations in the CPT-II deficiency, OCTN2 mutations in the Primary carnitine deficiency (PCD), and PNPLA2 mutations in Neutral Lipid Storage Myopathy (NLSDM). Fat oxidation is impaired in lipin-1 deficiency. The main morphological feature is the accumulation of lipid droplets in muscle and other tissues. An emerging role of specific microRNAs (myomiRs)  has been recently evidenced in myopathies. We investigated the role of myomiRs in RR-MADD and NLSDM patients.

We performed genetic analysis and measured serum myomiRs (miR-1, miR-206, miR-133a, miR-133b) of three RR-MADD patients and three patients pertaining to an NLSDM family.

We obtained muscle CT/ MRI and compared muscle imaging of muscle mass with an elevation of myomiRNAs in the patients and in control subjects. While RR-MADD patients were under carnitine/riboflavin treatment, NLSDM patients were without a specific treatment.

In all patient muscle biopsies,  LSM was observed.  As expected, Jordan's anomaly (i.e.lipid droplets in leukocytes) was detected in the three patients of NLSDM family. In these subjects, two novel PNPLA2 missense mutations were identified. The patients exhibited also a marked elevation of myomiRs in serum, in the range of 10-20 fold higher than that of control subjects. Two had an asymmetric upper or lower muscle distal atrophy, the third presented hepatomegaly. In RR-MADD patients three novel ETFDH mutations were found. MyomiRs profile was less upregulated but still inversely correlated to muscle mass.

In NLSDM and RR-MADD, the myomiRs represent an indicator of muscle atrophy and they might be useful to monitor evolution during pharmaceutical or physical treatment.

Study Supported :Telethon GGP14066.