Anti-LMNA monoclonal antibody, clone FQS5631

We herein report a case of a 28-year-old man with generalized lipodystrophy-associated progeroid syndrome treated by leptin replacement. He showed symptoms of generalized lipodystrophy around onset of puberty. His body mass index was 11.9 kg/m(2), and he had a short stature, birdlike facies, dental crowding due to micrognathia, partial graying and loss of hair, and a high-pitched voice, all of which are typical features of the progeroid syndrome. Laboratory examinations and abdominal ultrasonography revealed diabetes mellitus, insulin-resistance, dyslipidemia, decreased serum leptin levels (2.2 ng/mL), elevated serum hepatobiliaty enzyme levels and fatty liver. Whole exome sequencing revealed de novo heterozygous LMNA p.T10I mutation, indicating generalized lipodystrophy-associated progeroid syndrome, which is a newly identified subtype of atypical progeroid syndrome characterized by severe metabolic abnormalities. Daily injection of metreleptin [1.2 mg (0.04 mg/kg/day] was started. Metreleptin treatment significantly improved his diabetes from HbA1c 11.0% to 5.4% in six months. It also elevated serum testosterone levels. Elevated serum testosterone levels persisted even 1 year after the initiation of metreleptin treatment. To the best of our knowledge, this is the first Japanese case report of generalized lipodystrophy-associated progeroid syndrome. Furthermore, we evaluated short and long-term effectiveness of leptin replacement on generalized lipodystrophy by monitoring metabolic and endocrine profiles.

A 6-year-old girl was admitted to our hospital because of the presence of a slow-growing tumor in her right elbow. Biopsy specimens showed a round to spindle cell neoplasm with uncertain malignant potential, leading to the decision of surgical resection. Histologically, the resected tumor was encapsulated by fibrous tissue but focally invaded the surrounding skeletal muscles. The tumor was composed of ganglion cell like short spindle cells with lymphocytic infiltration in the collagenous background. Tumor cells with large bizarre nuclei were occasionally observed, and multinucleated giant cells were scattered at the periphery. Hemangiopericytoma-like patterns and adipose tissue elements were not evident, and mitotic figures were rarely observed (<1 per 10 high-power fields). Immunohistochemically, the tumor cells were positive for S-100 and CD34 and focally positive for epithelial membrane antigen and AE1/AE3. RNA sequencing and subsequent reverse-transcription polymerase chain reaction revealed alternative splicing forms of LMNA-NTRK1 fusion (Ex2-Ex10 and Ex2-Ex15). (C) 2017 Elsevier Inc. All rights reserved.