Effectiveness and Safety of Setmelanotide in a Patient With a Heterozygous PCSK1 Deficiency.
Ellina Lytvyak, Arshdeep Rattol, Eduardo Grunvald
✦ AI-curated · Sources linked
Case in brief
A 40-year-old female with a heterozygous PCSK1 N221D variant presented with severe early-onset treatment-resistant obesity. She had previously undergone bariatric surgery and tried conventional obesity medications with suboptimal results. After initiating treatment with setmelanotide, she achieved a total weight loss of 11.8% over three months, demonstrating the drug's effectiveness in this unique genetic context.
What made this case unusual
This case is notable for being the first report of severe skin hyperpigmentation as a cutaneous adverse effect of setmelanotide in a patient with a pathogenic PCSK1 variant.
Diagnostic / clinical pearl
Clinicians should consider the potential effectiveness of setmelanotide in patients with heterozygous PCSK1 mutations, despite previous treatment failures.
Why it matters
Understanding the response to setmelanotide in heterozygous mutations expands treatment options for patients with rare monogenic obesity conditions.