Endocrine Abstracts

Alström syndrome (ALMS) is a rare, autosomal recessive condition caused by variants in the ALMS1 gene. It is a multisystem, progressive condition characterised by vision (retinal dystrophy) and hearing loss, obesity, insulin resistance, type 2 diabetes mellitus, cardiomyopathy and renal dysfunction requiring specialist multidisciplinary management. Treatment of obesity in ALMS is challenging, with limited efficacy of glucagon-like peptide (GLP-1) receptor agonists and inconclusive results for the MC4R agonist, Setmelanotide. We present a case of an adolescent living with ALMS who has shown a successful response to Tirzepatide, a dual agonist for GLP-1 and Gastric Inhibitory Polypeptide (GIP) receptors. This male patient was born at term weighing 4.4 kg and developed early-onset, hyperphagic obesity. He was diagnosed with retinal dystrophy aged one year and moved to the United Kingdom aged 9 years, whilst being referred to a weight management service at 11 years. At that time his weight was 86.6 kg, height 162.5 cm, BMI 32.9 kg/m² (BMI-SDS +3.32). He was hypertensive, with evidence of metabolic dysfunction associated steatotic liver disease (MASLD), and significant visual impairment due to retinal dystrophy and was diagnosed with ALMS at 12 years of age. Despite behavioural and dietetic input from the multi-professional weight management team, he continued to gain weight. He initially commenced daily GLP-1 agonist therapy (Liraglutide) at 14 years of age but experienced further weight gain. Nine months later he was switched to Semaglutide, a weekly GLP-1 receptor agonist, for seven months, but weight gain persisted with no reported appetite change. Aged 17 years he was commenced on Tirzepatide (GLP-1 and GIP dual agonist) off-licence due to his obesity associated complications, with weight 122.7 kg, BMI 37.2 kg/m² (BMI SDS +3.77). Following, 6 months of treatment (5 mg weekly), he has lost 13.7 kg (11.2% weight loss, BMI-SDS reduction 0.84) with a corresponding drop in glycated haemoglobin (HbA1c) from 45 mmol/mol (NR<42) to 31 mmol/mol. The medication has been well tolerated with the patient reporting considerable reduction in appetite. With negligible reported benefits from Semaglutide and Setmelanotide in Alstrom’s syndrome, these early weight and appetite changes suggest possible benefits from dual agonist treatment which warrants further investigation in this condition.