Severe aortic stenosis during leptin replacement therapy in a patient with generalized lipodystrophy‐associated progeroid syndrome due to an LMNA variant: A case report

Abstract

ABSTRACT Leptin replacement therapy (LRT) has drastically improved the prognosis of patients with lipodystrophy, but pro‐inflammatory properties of leptin could become evident in the long term. Here, we report a 30‐year‐old Japanese woman with generalized lipodystrophy‐associated progeroid syndrome due to a heterozygous LMNA variant (c.29C > T; p.T10I), who was diagnosed with severe aortic stenosis (AS) after more than a decade of LRT, which required transcatheter aortic valve implantation. Given her marked hypoadiponectinemia and the LMNA variant, our patient might have been susceptible to progeria‐associated disorders, including aortic stenosis, which could have been exaggerated by the prolonged ‘imbalanced adipokines’ caused by LRT between pro‐inflammatory leptin and anti‐inflammatory adiponectin. Thus, long‐term LRT could be associated with AS in patients with the LMNA variant to cause generalized lipodystrophy‐associated progeroid syndrome and hypoadiponectinemia.

Keywords

• Adiponectin
• Generalized lipodystrophy‐associated progeroid syndrome
• Leptin replacement therapy