Metreleptin treatment for congenital generalized lipodystrophy type 4 (CGL4): a case report.

Abstract

.Congenital generalized lipodystrophy type 4 (CGL4) is a rare disease caused by mutations in the gene polymerase I and transcript release factor (PTRF), the main symptoms of which are systemic reductions in adipose tissue and muscular dystrophy. The strategy of treating CGL4 is to improve the insulin resistance and hypertriglyceridemia that result from systemic reductions in adipose tissue. Metreleptin, a synthetic analog of human leptin, is effective against generalized lipodystrophies; however, there are no reports of the use of metreleptin in the treatment of CGL4. Herein, we discuss the treatment of a six-year-old boy diagnosed with CGL4 due to a homozygous mutation in PTRF with metreleptin. His serum triglyceride level and homeostasis model assessment of insulin resistance (HOMA-IR) value decreased after two months of metreleptin treatment. However, the efficacy of metreleptin gradually decreased, and the treatment was suspended because anaphylaxis occurred after the dosage administered was increased. Subsequently, his serum triglyceride level and HOMA-IR value significantly increased. Anti-metreleptin-neutralizing antibodies were detected in his serum, which suggested that these antibodies reduced the efficacy of metreleptin and caused increased hypersensitivity. Thus, metreleptin appeared to be efficacious in the treatment of CGL4 in the short term, although an adverse immune response resulted in treatment suspension. Further studies are needed to evaluate metreleptin treatments for CGL4.