ESPE Abstracts

Introduction: Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive ciliopathy, with a prevalence of 1 in 100,000 – 160,000, caused by mutations across >20 known genes encoding for proteins responsible for the integrity of the primary cilium/basal body complex. Endocrinopathies associated with BBS include hypogonadism, hypothyroidism, and the metabolic complications of obesity. The endocrine characteristics of a large adult BBS cohort have been reported; however, there are fewer data reported in paediatric populations.

Objective: To describe the prevalence of endocrinopathies in BSS from a large paediatric cohort at a single-centre multidisciplinary service.

Method: A retrospective 13-year study of paediatric patients (<18 years) with genetically confirmed BBS at a single-centre paediatric multidisciplinary service. Patient data were collected from electronic records and an independent database, managed and developed by Certus Technology Associates. The study was registered and approved by the Hosptial Trust.

Results: Of 163 patients seen in the paediatric BBS clinic, 139 (50% female) had genetic confirmation and were included in analysis, where data were available. Mutations in BBS1 and BBS10 were most common, in 34% and 22%, respectively. Patients overweight/obese (BMI >1.34 SDs) totalled 128/136 (94%), and 110/136 (81%) were obese (BMI >2.05 SDs). Of patients >16 years, 26/30 (87%) were overweight/obese and 22/30 (73%) were obese. Type 2 diabetes was diagnosed in 3/139 (2%). Metformin was prescribed for 4/129 (3%) patients; two for diabetes, two for impaired glucose tolerance, and one for obesity. For patients >16 years, no patients had needed sex steroid treatment – all had spontaneous onset of puberty and no pubertal arrest. Of males, 8/39 (21%) had delayed puberty. Of females, 3/41 (7%) had delayed puberty, with mean age of menarche 12.9 years. Thyroid abnormalities were clinical hypothyroidism (on levothyroxine) in 2/125 (2%), subclinical hypothyroidism in 1/125 (1%), and 9/125 (7%) had abnormal thyroid function that self-resolved.

Conclusion: This is the largest analysis of endocrine outcomes for paediatric patients with BBS. Despite dietetic input in an MDT clinic, obesity remains a significant morbidity. Hypogonadism, hypothyroidism, and insulin resistance were not significant morbidities in this cohort and more prevalent in reports from adult cohorts. Longitudinal analysis of growth is ongoing. Longitudinal studies into adulthood could help better understand the timing of endocrinopathies associated with BSS, which could help service development and patient education.