GDF-15, a mitochondrial disease biomarker, is associated with the severity of multiple sclerosis.

GDF-15, a member of the transforming growth factor beta superfamily, regulates inflammatory and apoptotic pathways in various diseases, such as heart failure, kidney dysfunction, and cancer. We aimed to clarify potentially confounding variables affecting GDF-15 and demonstrate its utility as a mitochondrial biomarker using serum samples from 15 patients with mitochondrial diseases (MD), 15 patients with limbic encephalitis (LE), 10 patients with multiple sclerosis/neuromyelitis optica spectrum disorders (MS/NMOSD), and 19 patients with amyotrophic lateral sclerosis (ALS). GDF-15 and FGF-21 were significantly elevated in MD. GDF-15 and FGF-21 showed a good correlation in MD but not in LE, MS, and ALS. GDF-15 was potentially influenced by age in LE, MS/NMOSD, and ALS but not in MD. FGF-21 was not correlated with age in MS/NMOSD, ALS, LE, and MD. GDF-15 was not correlated with clinical features in LE or BMI or body weight in ALS. GDF-15 positively correlated with the Expanded Disability Status Scale (EDSS) in MS/NMOSD, while EDSS showed no correlation with age. In conclusion, the results revealed that GDF-15 may be influenced by EDSS in MS/NMOPSD and by age in LE, MS/NMOSD, and ALS but not in MD. Mitochondrial damage in MS/NMOSD is a potentially confounding variable affecting GDF-15.

[A representative case of joint contracture as a main feature of AL amyloid deposits identified in the skeletal muscles].

A 68-year-old man, with a history of type 2 diabetes mellitus and chronic kidney impairment, had been suffering from progressive knee joint contracture and dysesthesia of the lower extremities for 4 years. When he walked, his knees remained bent owing to contracture of the knee joints. There was no evidence of muscle pseudohypertrophy, intramuscular nodules, or muscle weakness. Clinical examination revealed IgA λ M-protein, reticular high-signal intensity lesions demonstrated by magnetic resonance T2-short TI IR(STIR) imaging of the lower extremity muscles, and a mixture of neurogenic and myogenic changes demonstrated by needle electromyography. A biopsy specimen from the vastus lateralis muscle identified Aλ amyloid deposits around the vessels, establishing a diagnosis of amyloid myopathy based on systemic AL amyloidosis. This case demonstrated that joint contracture and reticular lesions shown by magnetic resonance STIR imaging of the muscles can alert the physician to consider muscle biopsy to investigate deposition of amyloid in the skeletal muscles even in the absence of muscle pseudohypertrophy or weakness, both of which are characteristic of amyloid myopathy.

A Japanese case with Nasu-Hakola disease of DAP12 gene mutation exhibiting precuneus hypoperfusion.

A 38-year-old Japanese man with Nasu-Hakola disease (NHD) had repeated pathological fractures and frontal lobe symptoms which developed when he was 18 and 26 years old, respectively. Neuropsychological testing showed memory impairment, and in particular, visuo-spatial memory at the age of 35. Furthermore, single-photon emission computed tomography revealed precuneus hypoperfusion. The patient later suffered prolonged convulsive seizures, which left him in a persistent vegetative state. Genetic testing confirmed a heterozygous mutation in the DAP12 gene (a single-base deletion of 141 G in exon 3) specific to NHD. Precuneus dysfunction might contribute to characteristic memory impairment of NHD.