MON-717 - Bardet-Biedl Syndrome with Severe Obesity and Precocious Puberty: A Case Report

Introduction

Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder characterized by obesity, hypogonadism and other anomalies. This report describes the atypical case of a boy with severe obesity, precocious puberty, and an exceptional early weight loss following Topiramate treatment, with genetic testing confirming BBS.

Clinical Case

A 10-year-old male with a medical history of severe obesity, systemic arterial hypertension and anxiety was referred to our obesity center due to binge eating and hyperphagic behaviors. No other abnormalities were reported.

At first evaluation, he had heart rate 82 bpm, blood pressure 132/102 mmHg, weight 124 kg, height 155 cm, BMI 51.3 kg/m² (BMI Z-score 7.36), and mild acanthosis nigricans. He had Tanner stage G4P4, evidencing a previous premature and rapidly progressive pubertal development.

Abnormal metabolic findings included HOMA-IR of 11 (RV < 3), LDL 114 mg/dL (RV < 100). Basal hormonal measurements included LH 6.3 IU/L (pre-pubertal < 0.3), FSH 1.70 IU/L (pre-pubertal < 4), and testosterone 122 ng/dL (pre-pubertal < 40), confirming puberty onset.

On imaging studies, bone age was 17 years, evidencing a marked bone age advancement. Brain MRI and abdominal CT were normal.

Exome sequencing identified homozygous pathogenic variants in BBS1 gene (c.1169T>G; p.Met390Arg) and BBS2 gene (c.565C>T; p.Arg189*). No pathogenic variants were identified in genes related to precocious puberty.

Lifestyle recommendations included low-calorie diet and regular physical activity. Pharmacological therapy included Topiramate (initiated at 25 mg/day and titrated to 100 mg/day) and Metformin (1 g/day).

After an 11-month period of treatment, his weight dropped to 88.4 kg and BMI to 35.2 kg/m² (BMI Z-score 3.95). In addition, he had significant improvements in blood pressure (110/72 mmHg), LDL (87 mg/dL), insulin resistance (HOMA-IR of 5.3), binge eating and hyperphagic behavior. No side effects were reported.

Discussion

This case highlights an atypical presentation of BBS with precocious puberty without classical features. In addition, the patient had a remarkable weight loss with Topiramate treatment, with a weight reduction of 28.7% and an absolute BMI Z-score reduction of 3.41. A previous published case report identified a 22% weight loss in a patient with BBS with the combination of Topiramate and Phentermine for 8 months. Setmelanotide, the only FDA-approved medication for BBS treatment, has shown an average BMI Z-score decrease of 0.35. Further studies are necessary to assess the role of Topiramate in the management of obesity in patients with BBS.

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