Alström syndrome: an ultra-rare monogenic disorder as a model for insulin resistance, type 2 diabetes mellitus and obesity.
Alström syndrome
ENDO-ERN
Monogenetic diabetes
PBI-4050
Rare disease network
Setmelanotide
Journal
Endocrine
ISSN: 1559-0100
Titre abrégé: Endocrine
Pays: United States
ID NLM: 9434444
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
02
11
2020
accepted:
19
01
2021
pubmed:
11
2
2021
medline:
9
7
2021
entrez:
10
2
2021
Statut:
ppublish
Résumé
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. 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. 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. Managing a rare disease requires not only medical care but also a support network including patient associations.
Sections du résumé
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.
Identifiants
pubmed: 33566311
doi: 10.1007/s12020-021-02643-y
pii: 10.1007/s12020-021-02643-y
doi:
Substances chimiques
Cell Cycle Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
618-625Références
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)
pubmed: 13649370
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
doi: 10.1002/(sici)1096-8628(19971212)73:23.0.co;2-y
pubmed: 9409865
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
doi: 10.1038/ng867
pubmed: 11941369
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
doi: 10.1038/ng874
pubmed: 11941370
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
doi: 10.1038/sj.ejhg.5201933
pubmed: 17940554
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
doi: 10.1002/humu.22796
pubmed: 25846608
pmcid: 4475486
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
doi: 10.1002/humu.23233
pubmed: 28432734
pmcid: 5535005
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
doi: 10.1186/s13023-020-01468-8
pubmed: 32958032
pmcid: 7504843
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
doi: 10.1002/humu.20577
pubmed: 17594715
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
doi: 10.1001/archinte.165.6.675
pubmed: 15795345
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
doi: 10.2174/138920211795677912
pubmed: 22043170
pmcid: 3137007
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
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
doi: 10.2337/diabetes.54.5.1581
pubmed: 15855349
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
doi: 10.1371/journal.pgen.0030008
pubmed: 17206865
pmcid: 1761047
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
doi: 10.1091/mbc.E10-03-0246
pubmed: 20844083
pmcid: 2965680
F. Hildebrandt, T. Benzing, N. Katsanis, Ciliopathies. N. Engl. J. Med. 364(16), 1533–1543 (2011). https://doi.org/10.1056/NEJMra1010172
doi: 10.1056/NEJMra1010172
pubmed: 21506742
pmcid: 3640822
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
doi: 10.1038/s41556-020-0566-0
pubmed: 32868900
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
doi: 10.1242/jcs.130344
pubmed: 24681783
pmcid: 4038940
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
doi: 10.1186/s12864-016-2679-1
pubmed: 27142762
pmcid: 4855444
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
doi: 10.1371/journal.pone.0019081
pubmed: 21541333
pmcid: 3082548
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
doi: 10.2147/AGG.S74598
pubmed: 25705109
pmcid: 4334166
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
doi: 10.1016/j.cmet.2014.11.019
pubmed: 25543293
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
doi: 10.1371/journal.pone.0109540
pubmed: 25299671
pmcid: 4192353
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
doi: 10.1093/hmg/ddi235
pubmed: 16000322
pmcid: 2862911
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
doi: 10.1210/me.2005-0494
pubmed: 16513793
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
doi: 10.1093/hmg/ddv447
pubmed: 26494903
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
doi: 10.1093/hmg/ddz053
pubmed: 31220269
pmcid: 6586141
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
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
doi: 10.1371/journal.pone.0037925
pubmed: 22693585
pmcid: 3365098
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
doi: 10.1074/jbc.M801750200
pubmed: 18617516
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
doi: 10.1002/dneu.22031
pubmed: 22581473
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
doi: 10.1042/CS20160469
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)
pubmed: 18506366
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
doi: 10.1093/nar/gkl651
pubmed: 16973895
pmcid: 1635288
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
doi: 10.1210/jc.2018-00496
pubmed: 29718281
pmcid: 6276679
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
doi: 10.1111/j.1399-5448.2011.00789.x
pubmed: 21722283
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
doi: 10.1210/jc.2005-2633
pubmed: 16720663
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
doi: 10.1111/j.1399-5448.2010.00698.x
pubmed: 21518413
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
doi: 10.1016/S0161-6420(98)97033-6
pubmed: 9663233
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
doi: 10.1111/liv.13163
pubmed: 27178444
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
doi: 10.1111/j.1365-2265.2004.01952.x
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
doi: 10.1186/s13023-015-0366-y
pubmed: 26603037
pmcid: 4657378
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
doi: 10.1038/ejhg.2011.168
pubmed: 21897446
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
doi: 10.1002/ajmg.a.32730
pubmed: 19283853
pmcid: 2820246
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
doi: 10.1210/jc.2015-1577
pubmed: 26066530
pmcid: 4525001
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
doi: 10.1016/j.jhep.2020.02.006
pubmed: 32302728
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
doi: 10.1097/MOL.0b013e32832dd51a
pubmed: 19550324
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
doi: 10.1186/s12902-018-0315-6
pubmed: 30477455
pmcid: 6258144
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
doi: 10.1016/j.ajpath.2018.01.009
pubmed: 29454750
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
doi: 10.1016/j.molmed.2018.12.002
pubmed: 30642682
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
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
doi: 10.1007/s00467-007-0435-0
pubmed: 17357787
pmcid: 6904379
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
doi: 10.1038/ejhg.2012.115
pubmed: 22713813
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
doi: 10.3389/fped.2018.00023
pubmed: 29487844
pmcid: 5816783
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
doi: 10.1210/clinem/dgaa551