Abstract

Proopiomelanocortin (POMC) deficiency is a rare monogenic obesity syndrome typically characterized by early-onset obesity, red hair, and hypopigmentation, while linear growth is usually preserved. We report an adolescent girl with genetically confirmed POMC deficiency who developed short stature with biochemically confirmed growth hormone deficiency (GHD). She was diagnosed at 3.5 years of age with a homozygous c.64delA (p.Thr22Leufs*29) variant. Progressive growth deceleration became apparent after 12 years of age. At 13 years, her weight was 56.7 kg (+0.8 SDS), height was 143.0 cm (−2.5 SDS), and BMI was 27.1 kg/m² (+2.0 SDS). Growth velocity was 1.64 cm/year (−1.61 SDS), and pubertal stage was Tanner I. At 14 years of age, bone age was 10 years. IGF-1 was low at 82.8 µg/L (SDS: −2.28), and IGFBP-3 was 2.3 mg/L (SDS: −3.84). After euthyroidism had been achieved and estrogen priming had been completed, GH stimulation testing with L-DOPA and clonidine showed peak GH levels of 0.52 and 1.0 µg/L, respectively. Pituitary MRI was normal. Recombinant GH therapy (0.035 mg/kg/day) was initiated at 14 years 3 months. After 9 months, height increased to 150.2 cm (−1.95 SDS), BMI was 26.51 kg/m² (+1.79 SDS), and growth velocity improved to 11.29 cm/year, with no adverse events during follow-up. This case expands the clinical spectrum of POMC deficiency by demonstrating short stature with biochemically confirmed GHD and a notable early growth response to GH therapy. Further studies are needed to clarify the underlying mechanisms and to guide follow-up and management.