Endocrine Abstracts

Bardet-Biedl affects 1/100,000 people. Biallelic loss of function pathogenic variants in over 26 genes may be due to autosomal recessive inheritance. Diagnosis is clinical, with genetic testing confirmation. Presenting features include retinal cone-rod dystrophy, obesity, polydactyly, cognitive impairment, hypogonadism, genitourinary abnormalities, monogenic diabetes, hypothyroidism, polycystic ovarian and metabolic syndrome. We present a rare case of Bardet-Biedl type 3, with compound heterozygous pathogenic ARL6 gene variants. Initial genetics failed to identify an explanation with only one, classified benign variant, in exon 2 of the BBS10 gene identified. Further genetic investigation with a Bardet-Biedl and associated ciliopathy syndromes panel, identified two pathogenic variants in ARL6 gene. ADP Ribosylation Factor like GTPase 6 is a protein coding gene, associated with 5.1 % of all Bardet-Biedl cases. First presenting aged 16, with symptomatic hyperglycaemia, treatment was for presumed Type 1 diabetes. Other features however included polydactyly, central obesity, retinal dystrophy, intellectual disability, and PCOS. Referral to adult diabetes clinics age 29yrs allowed insulin discontinuation with dieting and metformin. Insulin reserve was confirmed (c-peptide 10.9 mg/l, negative anti GAD, IA2, ZnT8 antibodies). Endocrine referral in 2021 for secondary amenorrhea confirmed secondary hypogonadism from a partially empty sella on pituitary MRI. 63% of MRI pituitaries in Bardet-Biedl have abnormalities including pituitary hypoplasia, Rathke’s cyst, enlarged glands secondary to hyperprolactinemia, with primary or secondary hypogonadism. A fibroscan due to deranged liver function tests confirmed NASH cirrhosis from obesity associated insulin resistance. This case highlights the importance of extensive genetic testing for the appropriate diagnosis, management and counselling of patients with Bardet-Biedl syndrome and of the importance of clarifying the type of diabetes present through c-peptide and Anti GAD, IA2 and ZnT8 antibodies testing.