ESPE Abstracts

Background: Leptin, a hormone released from adipose tissue, exerts its influence through the leptin receptor located in the arcuate nucleus of the hypothalamus. Leptin receptor mutation is an extremely rare autosomal recessive monogenic disorder, caused by biallelic pathogenic variants in the LEPR gene. Individuals with leptin receptor deficiency exhibit rapid weight gain, severe early-onset obesity, hyperphagia, hypogonadotrophic hypogonadism, and T-cell abnormalities. Setmelanotide is a U.S. FDA approved drug which could be used for management of obesity in those patients above the age of 6 years. To date, there are less than 60 patients with reported LEPR gene mutation. To our knowledge, only 6 patients have been reported from Egypt so far.

Case report: Herein, we describe a 3.6-year-old boy presenting with progressive weight gain starting at the age of 6 months along with hyperphagia, and infantile Blount’s disease. He was conceived through Intracytoplasmic sperm injection (ICSI). He was born to consanguineous parents, at term, with a birth weight of 3 kg. He has a twin sister with normal weight. He had a family history of obesity and diabetes mellitus. By physical examination, his weight was 44 kg (+5.95 SD), height was 103 cm (+0.75 SD), and BMI 41.5 (>99.9^th percentile). He had generalized pattern of fat distribution, normal blood pressure, no acanthosis nigricans, or stria. He had normal stretched penile length. There were no features suggestive of any syndromic disease. Ophthalmological examination was normal. He had obstructive sleep apnea and daytime somnolence, which improved after adenoidectomy. Laboratory investigations showed impaired fasting blood glucose level (108 mg/dl), elevated HOMA-IR, normal HbA1c, subclinical hypothyroidism, and markedly raised serum leptin levels (92.3 ng/ml). Whole-exome-sequencing revealed LEPR gene mutation.

Conclusion: Congenital deficiency of leptin receptor is a very rare cause of severe early-onset obesity, which can lead to infantile Blount's disease. Earlier diagnosis of rare forms of monogenic obesity through genetic testing -especially in consanguineous families- is important, as it can improve genetic counseling and patients can benefit from the new targeted therapies.