Skip to main content

Advertisement

SpringerLink
Log in

Alström syndrome: an ultra-rare monogenic disorder as a model for insulin resistance, type 2 diabetes mellitus and obesity

  • Review
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Background

Alström syndrome (ALMS) is a monogenic ultra-rare disorder with a prevalence of one per million inhabitants caused by pathogenic variants of ALMS1 gene. ALMS1 is located on chromosome 2p13, spans 23 exons and encodes a predicted 461.2-kDa protein of 4169 amino acids. The infantile cone-rod dystrophy with nystagmus and severe visual impairment is the earliest and most consistent clinical manifestation of ALMS. In addition, infantile transient cardiomyopathy, early childhood obesity with hyperphagia, deafness, insulin resistance (IR), type 2 diabetes mellitus (T2DM), systemic fibrosis and progressive renal or liver dysfunction are common findings. ALMS1 encodes a large ubiquitously expressed protein that is associated with the centrosome and the basal body of primary cilium.

Current research

The localisation of ALMS1 to the ciliary basal body suggests its contribution to ciliogenesis and/or normal ciliary function, or centriolar stability. ALMS1 regulate glucose transport through the actin cytoskeleton, which plays an important role in insulin-stimulated GLUT4 transport. Both extreme IR and β-cell failure are the two determinant factors responsible for the development of glucose metabolism alterations in ALMS.

Treatment

Currently, there is no known cure for ALMS other than managing the underlying systemic diseases. When possible, individuals with ALMS and families should be referred to a centre of expertise and followed by a multidisciplinary team. Lifestyle modification, aerobic exercise and dietary induced weight loss are highly recommended as primary treatment for ALMS patients with T2DM and obesity.

Conclusion

Managing a rare disease requires not only medical care but also a support network including patient associations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. C.H. Alstrom, B. Hallgren, L.B. Nilsson, H. Asander, Retinal degeneration combined with obesity, diabetes mellitus and neurogenous deafness: a specific syndrome (not hitherto described) distinct from the Laurence-Moon-BBS: a clinical, endocrinological and genetic examination based on a large pedigree. Acta Psychiatr. Neurol. Scand Suppl. 129, 1–35 (1959)

    CAS  PubMed  Google Scholar 

  2. J.D. Marshall, M.D. Ludman, S.E. Shea, S.R. Salisbury, S.M. Willi, R.G. LaRoche, P.M. Nishina, Genealogy, natural history, and phenotype of Alström syndrome in a large Acadian kindred and three additional families. Am. J. Med. Genet. 73(2), 150–161 (1997). https://doi.org/10.1002/(sici)1096-8628(19971212)73:23.0.co;2-y

    Article  CAS  PubMed  Google Scholar 

  3. G.B. Collin, J.D. Marshall, A. Ikeda, W.V. So, I. Russell-Eggitt, P. Maffei, S. Beck, C.F. Boerkoel, N. Sicolo, M. Martin, P.M. Nishina, J.K. Naggert, Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome. Nat. Genet. 31(1), 74–78 (2002). https://doi.org/10.1038/ng867

    Article  CAS  PubMed  Google Scholar 

  4. T. Hearn, G.L. Renforth, C. Spalluto, N.A. Hanley, K. Piper, S. Brickwood, C. White, V. Connolly, J.F. Taylor, I. Russell-Eggitt, D. Bonneau, M. Walker, D.I. Wilson, Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alström syndrome. Nat. Genet. 31(1), 79–83 (2002). https://doi.org/10.1038/ng874

    Article  CAS  PubMed  Google Scholar 

  5. J.D. Marshall, S. Beck, P. Maffei, J.K. Naggert, Alström syndrome. Eur. J. Hum. Genet. 15(12), 1193–1202 (2007). https://doi.org/10.1038/sj.ejhg.5201933

    Article  CAS  PubMed  Google Scholar 

  6. J.D. Marshall, J. Muller, G.B. Collin, G. Milan, S.F. Kingsmore, D. Dinwiddie, E.G. Farrow, N.A. Miller, F. Favaretto, P. Maffei, H. Dollfus, R. Vettor, J.K. Naggert, Alström syndrome: mutation spectrum of ALMS1. Hum. Mutat. 36(7), 660–638 (2015). https://doi.org/10.1002/humu.22796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. D. Astuti, A. Sabir, P. Fulton, M. Zatyka, D. Williams, C. Hardy, G. Milan, F. Favaretto, P. Yu-Wai-Man, J. Rohayem, M. López de Heredia, T. Hershey, L. Tranebjaerg, J.H. Chen, A. Chaussenot, V. Nunes, B. Marshall, S. McAfferty, V. Tillmann, P. Maffei, V.,G. Paquis-Flucklinger, Monogenic diabetes syndromes: locus-specific databases for Alström, Wolfram, and Thiamine-responsive megaloblastic anemia. Hum. Mutat. 38(7), 764–777 (2017). https://doi.org/10.1002/humu.23233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. N. Tahani, P. Maffei, H. Dollfus, R. Paisey, D. Valverde, G. Milan, J.C. Han, F. Favaretto, S.C. Madathil, C. Dawson, M.J. Armstrong, A.T. Warfield, S. Düzenli, C.A. Francomano, M. Gunay-Aygun, F. Dassie, V. Marion, M. Valenti, K. Leeson-Beevers, A. Chivers, R. Steeds, T. Barrett et al., Consensus clinical management guidelines for Alström syndrome. Orphanet J. Rare Dis. 15(1), 253 (2020). https://doi.org/10.1186/s13023-020-01468-8

    Article  PubMed  PubMed Central  Google Scholar 

  9. J.D. Marshall, E.G. Hinman, G.B. Collin, S. Beck, R. Cerqueira, P. Maffei, G. Milan, W. Zhang, D.I. Wilson, T. Hearn, P. Tavares, R. Vettor, C. Veronese, M. Martin, W.V. So, P.M. Nishina, J.K. Naggert, Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. Hum. Mutat. 28(11), 1114–1123 (2007). https://doi.org/10.1002/humu.20577

    Article  CAS  PubMed  Google Scholar 

  10. J.D. Marshall, R.T. Bronson, G.B. Collin, A.D. Nordstrom, P. Maffei, R.B. Paisey, C. Carey, S. Macdermott, I. Russell-Eggitt, S.E. Shea, J. Davis, S. Beck, G. Shatirishvili, C.M. Mihai, M. Hoeltzenbein, G.B. Pozzan, I. Hopkinson, N. Sicolo, J.K. Naggert, P.M. Nishina, New Alström syndrome phenotypes based on the evaluation of 182 cases. Arch. Intern. Med. 165(6), 675–683 (2005). https://doi.org/10.1001/archinte.165.6.675

    Article  PubMed  Google Scholar 

  11. J.D. Marshall, P. Maffei, G.B. Collin, J.K. Naggert, Alström syndrome: genetics and clinical overview. Curr. Genomics 12(3), 225–235 (2011). https://doi.org/10.2174/138920211795677912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. F. Dassie, R. Lorusso, S. Benavides-Varela, G. Milan, F. Favaretto, E. Callus, S. Cagnin, F. Reggiani, G. Minervini, S. Tosatto, R. Vettor, C. Semenza, P. Maffei, Neurocognitive assessment and DNA sequencing expand the phenotype and genotype spectrum of Alström syndrome. Am. J. Med Genet. A (2021). https://doi.org/10.1002/ajmg.a.62029

  13. T. Hearn, C. Spalluto, V.J. Phillips, G.L. Renforth, N. Copin, N.A. Hanley, D.I. Wilson, Subcellular localization of ALMS1 supports involvement of centrosome and basal body dysfunction in the pathogenesis of obesity, insulin resistance, and type 2 diabetes. Diabetes 54(5), 1581–1587 (2005). https://doi.org/10.2337/diabetes.54.5.1581

    Article  CAS  PubMed  Google Scholar 

  14. G. Li, R. Vega, K. Nelms, N. Gekakis, C. Goodnow, P. McNamara, H. Wu, N.A. Hong, R. Glynne, A role for Alström syndrome protein, alms1, in kidney ciliogenesis and cellular quiescence. PLoS Genet. 3(1), e8 (2007). https://doi.org/10.1371/journal.pgen.0030008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. V.J. Knorz, C. Spalluto, M. Lessard, T.L. Purvis, F.F. Adigun, G.B. Collin, N.A. Hanley, D.I. Wilson, T. Hearn, Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731. Mol. Biol. Cell 21(21), 3617–3629 (2010). https://doi.org/10.1091/mbc.E10-03-0246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. F. Hildebrandt, T. Benzing, N. Katsanis, Ciliopathies. N. Engl. J. Med. 364(16), 1533–1543 (2011). https://doi.org/10.1056/NEJMra1010172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. C. Miceli, F. Roccio, L. Penalva-Mousset, M. Burtin, C. Leroy, I. Nemazanyy, N. Kuperwasser, M. Pontoglio, G. Friedlander, E. Morel, F. Terzi, P. Codogno, N. Dupont, The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation of kidney epithelial cells. Nat. Cell Biol. 22(9), 1091–1102 (2020). https://doi.org/10.1038/s41556-020-0566-0

    Article  CAS  PubMed  Google Scholar 

  18. C.C. Leitch, S. Lodh, V. Prieto-Echagüe, J.L. Badano, N.A. Zaghloul, Basal body proteins regulate Notch signaling through endosomal trafficking. J. Cell Sci. 127(Pt 11), 2407–2419 (2014). https://doi.org/10.1242/jcs.130344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. T.L. Hostelley, S. Lodh, N.A. Zaghloul, Whole organism transcriptome analysis of zebrafish models of Bardet-Biedl Syndrome and Alström Syndrome provides mechanistic insight into shared and divergent phenotypes. BMC Genomics 17, 318 (2016). https://doi.org/10.1186/s12864-016-2679-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. E. Zulato, F. Favaretto, C. Veronese, S. Campanaro, J.D. Marshall, S. Romano, A. Cabrelle, G.B. Collin, B. Zavan, A.S. Belloni, E. Rampazzo, J.K. Naggert, G. Abatangelo, N. Sicolo, P. Maffei, G. Milan, R. Vettor, ALMS1-deficient fibroblasts over-express extra-cellular matrix components, display cell cycle delay and are resistant to apoptosis. PLoS ONE 6(4), e19081 (2011). https://doi.org/10.1371/journal.pone.0019081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. M.G. Butler, K. Wang, J.D. Marshall, J.K. Naggert, J.A. Rethmeyer, S.S. Gunewardena, A.M. Manzardo, Coding and noncoding expression patterns associated with rare obesity-related disorders: Prader-Willi and Alström syndromes. Adv. Genomics Genet. 2015(5), 53–75 (2015). https://doi.org/10.2147/AGG.S74598

    Article  PubMed  PubMed Central  Google Scholar 

  22. E.C. Oh, S. Vasanth, N. Katsanis, Metabolic regulation and energy homeostasis through the primary Cilium. Cell Metab. 21(1), 21–31 (2015). https://doi.org/10.1016/j.cmet.2014.11.019

    Article  CAS  PubMed  Google Scholar 

  23. F. Favaretto, G. Milan, G.B. Collin, J.D. Marshall, F. Stasi, P. Maffei, R. Vettor, J.K. Naggert, GLUT4 defects in adipose tissue are early signs of metabolic alterations in Alms1GT/GT, a mouse model for obesity and insulin resistance. PLoS ONE 9(10), e109540 (2014). https://doi.org/10.1371/journal.pone.0109540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. G.B. Collin, E. Cyr, R. Bronson, J.D. Marshall, E.J. Gifford, W. Hicks, S.A. Murray, Q.Y. Zheng, R.S. Smith, P.M. Nishina, J.K. Naggert, Alms1-disrupted mice recapitulate human Alström syndrome. Hum. Mol. Genet. 14(16), 2323–2333 (2005). https://doi.org/10.1093/hmg/ddi235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. T. Arsov, D.G. Silva, M.K. O’Bryan, A. Sainsbury, N.J. Lee, C. Kennedy, S.S. Manji, K. Nelms, C. Liu, C.G. Vinuesa, D.M. de Kretser, C.C. Goodnow, N. Petrovsky, Fat aussie—a new Alström syndrome mouse showing a critical role for ALMS1 in obesity, diabetes, and spermatogenesis. Mol. Endocrinol. 20(7), 1610–1622 (2006). https://doi.org/10.1210/me.2005-0494

    Article  CAS  PubMed  Google Scholar 

  26. S. Lodh, T.L. Hostelley, C.C. Leitch, E.A. O’Hare, N.A. Zaghloul, Differential effects on β-cell mass by disruption of Bardet-Biedl syndrome or Alstrom syndrome genes. Hum. Mol. Genet. 25(1), 57–68 (2016). https://doi.org/10.1093/hmg/ddv447

    Article  CAS  PubMed  Google Scholar 

  27. J.E. Nesmith, T.L. Hostelley, C.C. Leitch, M.S. Matern, S. Sethna, R. McFarland, S. Lodh, C.J. Westlake, R. Hertzano, Z.M. Ahmed, N.A. Zaghloul, Genomic knockout of alms1 in zebrafish recapitulates Alström syndrome and provides insight into metabolic phenotypes. Hum. Mol. Genet. 28(13), 2212–2223 (2019). https://doi.org/10.1093/hmg/ddz053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. T. Geberhiwot, S. Baig, C. Obringer, D. Girard, C. Dawson, K. Manolopoulos, N. Messaddeq, P. Bel Lassen, K. Clement, J.W. Tomlinson, R.P. Steeds, H. Dollfus, N. Petrovsky, V. Marion, Relative adipose tissue failure in Alström syndrome drives obesity-induced insulin resistance. Diabetes, db200647 (2020). https://doi.org/10.2337/db20-0647

  29. G.B. Collin, J.D. Marshall, B.L. King, G. Milan, P. Maffei, D.J. Jagger, J.K. Naggert, The Alström syndrome protein, ALMS1, interacts with α-actinin and components of the endosome recycling pathway. PLoS ONE 7(5), e37925 (2012). https://doi.org/10.1371/journal.pone.0037925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. I. Talior-Volodarsky, V.K. Randhawa, H. Zaid, A. Klip, Alpha-actinin-4 is selectively required for insulin-induced GLUT4 translocation. J. Biol. Chem. 283(37), 25115–25123 (2008). https://doi.org/10.1074/jbc.M801750200

    Article  CAS  PubMed  Google Scholar 

  31. D. Heydet, L.X. Chen, C.Z. Larter, C. Inglis, M.A. Silverman, G.C. Farrell, M.R. Leroux, A truncating mutation of Alms1 reduces the number of hypothalamic neuronal cilia in obese mice. Dev. Neurobiol. 73(1), 1–13 (2013). https://doi.org/10.1002/dneu.22031

    Article  CAS  PubMed  Google Scholar 

  32. L. Poekes, V. Legry, O. Schakman, C. Detrembleur, A. Bol, Y. Horsmans, G.C. Farrell, I.A. Leclercq, Defective adaptive thermogenesis contributes to metabolic syndrome and liver steatosis in obese mice. Clin. Sci. 131(4), 285–296 (2017). https://doi.org/10.1042/CS20160469

    Article  CAS  Google Scholar 

  33. S. Romano, G. Milan, C. Veronese, G.B. Collin, J.D. Marshall, C. Centobene, F. Favaretto, C. Dal Pra, A. Scarda, S. Leandri, J.K. Naggert, P. Maffei, R. Vettor, Regulation of Alström syndrome gene expression during adipogenesis and its relationship with fat cell insulin sensitivity. Int J. Mol. Med. 21(6), 731–736 (2008)

    CAS  PubMed  Google Scholar 

  34. N. Yabuta, H. Onda, M. Watanabe, N. Yoshioka, I. Nagamori, T. Funatsu, S. Toji, K. Tamai, H. Nojima, Isolation and characterization of the TIGA genes, whose transcripts are induced by growth arrest. Nucleic Acids Res. 34(17), 4878–4892 (2006). https://doi.org/10.1093/nar/gkl651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. J.C. Han, D.P. Reyes-Capo, C.Y. Liu, J.C. Reynolds, E. Turkbey, I.B. Turkbey, J. Bryant, J.D. Marshall, J.K. Naggert, W.A. Gahl, J.A. Yanovski, M. Gunay-Aygun, Comprehensive endocrine-metabolic evaluation of patients with Alström syndrome compared with BMi-matched controls. J. Clin. Endocrinol. Metab. 103(7), 2707–2719 (2018). https://doi.org/10.1210/jc.2018-00496

    Article  PubMed  PubMed Central  Google Scholar 

  36. V. Bettini, P. Maffei, C. Pagano, S. Romano, G. Milan, F. Favaretto, J.D. Marshall, R. Paisey, F. Scolari, N.A. Greggio, I. Tosetto, J.K. Naggert, N. Sicolo, R. Vettor, The progression from obesity to type 2 diabetes in Alström syndrome. Pediatr. Diabetes 13(1), 59–67 (2012). https://doi.org/10.1111/j.1399-5448.2011.00789.x

    Article  CAS  PubMed  Google Scholar 

  37. J.A. Minton, K.R. Owen, C.J. Ricketts, N. Crabtree, G. Shaikh, S. Ehtisham, J.R. Porter, C. Carey, D. Hodge, R. Paisey, M. Walker, T.G. Barrett, Syndromic obesity and diabetes: changes in body composition with age and mutation analysis of ALMS1 in 12 United Kingdom kindreds with Alstrom syndrome. J. Clin. Endocrinol. Metab. 91(8), 3110–3116 (2006). https://doi.org/10.1210/jc.2005-2633

    Article  CAS  PubMed  Google Scholar 

  38. A. Mokashi, E.A. Cummings, Presentation and course of diabetes in children and adolescents with Alstrom syndrome. Pediatr. Diabetes 12(3 Pt 2), 270–275 (2011). https://doi.org/10.1111/j.1399-5448.2010.00698.x

    Article  PubMed  Google Scholar 

  39. I.M. Russell-Eggitt, P.T. Clayton, R. Coffey, A. Kriss, D.S. Taylor, J.F. Taylor, Alström syndrome. Report of 22 cases and literature review. Ophthalmology 105(7), 1274–1280 (1998). https://doi.org/10.1016/S0161-6420(98)97033-6

    Article  CAS  PubMed  Google Scholar 

  40. L.L. Gathercole, J.M. Hazlehurst, M.J. Armstrong, R. Crowley, S. Boocock, M.W. O’Reilly, M. Round, R. Brown, S. Bolton, R. Cramb, P.N. Newsome, R.K. Semple, R. Paisey, J.W. Tomlinson, T. Geberhiwot, Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alström syndrome. Liver Int. 36(11), 1704–1712 (2016). https://doi.org/10.1111/liv.13163

    Article  CAS  PubMed  Google Scholar 

  41. R.B. Paisey, C.M. Carey, L. Bower, J. Marshall, P. Taylor, P. Maffei, P. Mansell, Hypertriglyceridaemia in Alström’s syndrome: causes and associations in 37 cases. Clin. Endocrinol. 60(2), 228–231 (2004). https://doi.org/10.1111/j.1365-2265.2004.01952.x

    Article  CAS  Google Scholar 

  42. S. Van Groenendael, L. Giacovazzi, F. Davison, O. Holtkemper, Z. Huang, Q. Wang, K. Parkinson, T. Barrett, T. Geberhiwot, High quality, patient centred and coordinated care for Alstrom syndrome: a model of care for an ultra-rare disease. Orphanet J. Rare Dis. 10, 149 (2015). https://doi.org/10.1186/s13023-015-0366-y

    Article  PubMed  PubMed Central  Google Scholar 

  43. K. Jatti, R. Paisey, R. More, Coronary artery disease in Alström syndrome. Eur. J. Hum. Genet. 20(1), 117–118 (2012). https://doi.org/10.1038/ejhg.2011.168

    Article  CAS  PubMed  Google Scholar 

  44. N.C. Lee, J.D. Marshall, G.B. Collin, J.K. Naggert, Y.H. Chien, W.Y. Tsai, W.L. Hwu, Caloric restriction in Alström syndrome prevents hyperinsulinemia. Am. J. Med. Genet. A 149A(4), 666–668 (2009). https://doi.org/10.1002/ajmg.a.32730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. R.B. Paisey, J. Smith, C. Carey, T. Barrett, F. Campbell, P. Maffei, J.D. Marshall, C. Paisey, R.P. Steeds, N.C. Edwards, S. Bunce, T. Geberhiwot, Duration of diabetes predicts aortic pulse wave velocity and vascular events in Alström syndrome. J. Clin. Endocrinol. Metab. 100(8), E1116–E1124 (2015). https://doi.org/10.1210/jc.2015-1577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. A. Arfianti, S. Pok, V. Barn, W.G. Haigh, M.M. Yeh, G.N. Ioannou, N.C. Teoh, G.C. Farrell, Exercise retards hepatocarcinogenesis in obese mice independently of weight control. J. Hepatol. 73(1), 140–148 (2020). https://doi.org/10.1016/j.jhep.2020.02.006

    Article  CAS  PubMed  Google Scholar 

  47. R.B. Paisey, New insights and therapies for the metabolic consequences of Alström syndrome. Curr. Opin. Lipidol. 20(4), 315–320 (2009). https://doi.org/10.1097/MOL.0b013e32832dd51a

    Article  CAS  PubMed  Google Scholar 

  48. S. Baig, V. Veeranna, S. Bolton, N. Edwards, J.W. Tomlinson, K. Manolopoulos, J. Moran, R.P. Steeds, T. Geberhiwot, Treatment with PBI-4050 in patients with Alström syndrome: study protocol for a phase 2, single-Centre, single-arm, open-label trial. BMC Endocr. Disord. 18(1), 88 (2018). https://doi.org/10.1186/s12902-018-0315-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. L. Gagnon, M. Leduc, J.F. Thibodeau, M.Z. Zhang, B. Grouix, F. Sarra-Bournet, W. Gagnon, K. Hince, M. Tremblay, L. Geerts, C.R.J. Kennedy, R.L. Hébert, A. Gutsol, C.E. Holterman, E. Kamto, L. Gervais, J. Ouboudinar, J. Richard, A. Felton, A. Laverdure, J.C. Simard, S. Létourneau, A newly discovered antifibrotic pathway regulated by two fatty acid receptors: GPR40 and GPR84. Am. J. Pathol. 188(5), 1132–1148 (2018). https://doi.org/10.1016/j.ajpath.2018.01.009

    Article  CAS  PubMed  Google Scholar 

  50. P. Kühnen, H. Krude, H. Biebermann, Melanocortin-4 receptor signalling: importance for weight regulation and obesity treatment. Trends Mol. Med. 25(2), 136–148 (2019). https://doi.org/10.1016/j.molmed.2018.12.002

    Article  CAS  PubMed  Google Scholar 

  51. R. Haws, S. Brady, E. Davis, K. Fletty, G. Yuan, G. Gordon, M. Stewart, J. Yanovski, Effect of setmelanotide, a melanocortin-4 receptor agonist, on obesity in Bardet-Biedl syndrome. Diabetes Obes. Metab. 22(11), 2133–2140. https://doi.org/10.1111/dom.14133

  52. J.L. Tobin, P.L. Beales, Bardet-Biedl syndrome: beyond the cilium. Pediatr. Nephrol. 22(7), 926–936 (2007). https://doi.org/10.1007/s00467-007-0435-0

    Article  PubMed  PubMed Central  Google Scholar 

  53. E. Forsythe, P.L. Beales, Bardet-Biedl syndrome. Eur. J. Hum. Genet. 21(1), 8–13 (2013). https://doi.org/10.1038/ejhg.2012.115

    Article  CAS  PubMed  Google Scholar 

  54. E. Forsythe, J. Kenny, C. Bacchelli, P.L. Beales, Managing Bardet-Biedl syndrome-now and in the future. Front. Pediatr. 6, 23 (2018). https://doi.org/10.3389/fped.2018.00023

    Article  PubMed  PubMed Central  Google Scholar 

  55. K. Isabelle, M. Manuel, M. Nadia, B. Jean-Jacques, C. Catherine, M. Jean, Z.B. Anna, G. Nathalie, D. Hélène, R. Sylvie, Reproduction function in male patients with Bardet Biedl syndrome. J. Clin. Endocrinol. Metab. 105(12), e4417–e4429 (2020). https://doi.org/10.1210/clinem/dgaa551

    Article  Google Scholar 

Download references

Acknowledgements

The authors would also like to thank the European Society of Endocrinology and the European Society for Paediatric Endocrinology for their generous support.

Funding

This publication is part of the project “777215/EuRRECa”, which has received funding from the European Union Health Programme (2014–2020).

Author information

Authors and Affiliations

  1. Department of Medicine (DIMED), Clinica Medica 3, Padua University Hospital, Padua, Italy

    Francesca Dassie, Francesca Favaretto, Silvia Bettini, Matteo Parolin, Roberto Vettor, Gabriella Milan & Pietro Maffei

  2. Italian Association of Alström Syndrome Patients—ASS.A.I., Endo-ERN ePAG, Padua, Italy

    Marina Valenti

  3. Department of General Pediatrics, Endocrinology/Diabetology and Clinical Research, Children’s Hospital Auf der Bult, Hannover, Germany

    Felix Reschke & Thomas Danne

Authors
  1. Francesca Dassie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesca Favaretto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silvia Bettini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matteo Parolin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marina Valenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Felix Reschke
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Thomas Danne
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Roberto Vettor
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gabriella Milan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pietro Maffei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pietro Maffei.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dassie, F., Favaretto, F., Bettini, S. et al. Alström syndrome: an ultra-rare monogenic disorder as a model for insulin resistance, type 2 diabetes mellitus and obesity. Endocrine 71, 618–625 (2021). https://doi.org/10.1007/s12020-021-02643-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-021-02643-y

Keywords

Search

Navigation