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Alström Syndrome (ALMS) is an ultra-rare multisystem genetic disorder caused by autosomal recessive variants in the ALMS1 gene, which is located on chromosome 2p13. ALMS is a multisystem, progressive disease characterised by visual disturbance, hearing impairment, cardiomyopathy, childhood obesity, extreme insulin resistance, accelerated non-alcoholic fatty liver disease (NAFLD), renal dysfunction, respiratory disease, endocrine and urologic disorders. Clinical symptoms first appear in infancy with great variability in age of onset and severity. ALMS has an estimated incidence of 1 case per 1,000,000 live births and ethnically or geographically isolated populations have a higher-than-average frequency. The rarity and complexity of the syndrome and the lack of expertise can lead to delayed diagnosis, misdiagnosis and inadequate care. Multidisciplinary and multiprofessional teams of experts are essential for the management of patients with ALMS, as early diagnosis and intervention can slow the progression of multi-organ dysfunctions and improve patient quality of life.These guidelines are intended to define standard of care for patients suspected or diagnosed with ALMS of any age. All information contained in this document has originated from a systematic review of the literature and the experiences of the authors in their care of patients with ALMS. The Appraisal of Guidelines for Research & Evaluation (AGREE II) system was adopted for the development of the guidelines and for defining the related levels of evidence and strengths of recommendations.These guidelines are addressed to: a) specialist centres, other hospital-based medical teams and staffs involved with the care of ALMS patients, b) family physicians and other primary caregivers and c) patients and their families.

Alström syndrome (ALMS) is an ultra-rare metabolic disorder caused by biallelic loss-of-function in the Alms1 gene which encodes a ubiquitously expressed centrosomal protein of the primary cilium. Although ALMS is characterised by several metabolic and hormonal dysfunctions that can lead to an increased risk of developing osteoporosis and bone fracture, an increased BMD have been observed. The aim of this study was to characterise the anthropometric, clinical, genetic and densitometric features of bone health in a large adult UK cohort of subjects with ALMS. Twenty-three patients with ALMS and 23 age-matched male control subjects were recruited. Lumbar spine (LS) and total hip (TH) bone mineral density (BMD) were evaluated by DXA in all subjects. A CT scan to assess the spinal bone architecture was performed in ALMS patients with raised lumbar density. Blood analysis for biochemical parameters and thyroid and sex hormones was performed in all ALMS patients. LS Z-score levels were higher than +2 SD in 35% of all ALMS study participants, of whom 75% were men and 25% were women. TH Z-scores were higher than +1 SD 13% of patients and all of them have higher than expected lumbar Z-score. An extremely high BMD was found in two of the oldest patients (LS Z-score +10.8 and +15.3 SD). ALMS patients tend to have high levels of BMD that increase with age, in particular of the trabecular bones. Although obesity and lifelong IR can be responsible for the increase in BMD, at least in part, of a possible signalling role of Alms1 protein as a bone-forming factor is plausible. • Alström syndrome is a monogenic metabolic disorder due to loss-of-function in the Alms1 gene. • Alström patients tend to have an increased BMD, especially at the trabecular bones. • Bone changes increase with age and are more evident in men Alström patients. • A possible signalling role of alms1 protein as a bone-forming factor is plausible. [ABSTRACT FROM AUTHOR]