ESPE Abstracts

Background: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited ciliopathy with pathogenic variants in at least 26 BBS genes. It affects multiple organs including kidney and liver; however, organ involvement differs widely regarding extent and time of first manifestation. Structural renal anomalies are an early feature with a frequency of > 50% and end-stage kidney disease (ESKD) cumulates to 25% in adolescence. Early-onset hyperphagia-associated obesity is another major symptom and contributes to liver pathology, presenting as steatosis/fibrosis. Aim of this study is to evaluate the potential of high-end ultrasound (US) regarding liver and kidney involvement in BBS.

Methods: Patients with genetically confirmed BBS were recruited from the University Children’s Hospital of Essen and from BBS patient days hosted in Germany. Clinical and laboratory data were extracted from patients’ digital records or medical letters US including shear wave elastography (SWE), dispersion (SWD), and attenuation imaging (ATI) were utilized.

Results: 49 BBS patients (24/49 male; aged 1.1–51.0 years, mean 17.8 years) were included in the study. Mean body weight (SDS 2.13 ± 1.33) and BMI (SDS 2.64 ± 1.18) were increased. Structural kidney abnormalities (dysplasia, cysts) were present in 75% (36/48). Renal function was impaired in 27% (13/49) and 3/13 had ESKD. In 51% (25/49) ATI of liver tissue was increased, indicating hepatic steatosis, and correlated with BMI SDS, liver size, and enzymes. SWE was elevated in 61% (30/49) suggesting hepatic fibrosis and was associated with BMI and GGT. Patients with pathogenic variants in BBS10 showed a tendency towards higher ATI and reduced GFR, and had significantly higher BMI SDS.

Conclusion: We detected abnormalities of the kidney and liver in a higher percentage of BBS patients than previously reported, indicating a high sensitivity of the evaluated US applications. ATI detected liver pathology early (partially prior to liver enzymes) and revealed differences related to the affected genes. Evidence of tissue pathology at an early stage may improve diagnostics. Moreover, high-end ultrasound and its new applications may contribute to the evaluation of therapeutic approaches. Patients from this cohort qualifying for treatment with the Melanocortin-4-Receptor (MC4R) agonist setmelanotide will prospectively be followed concerning the impact of treatment on their kidney and liver abnormalities. Results will be presented upon availability.