Syndromic Obesity and Diabetes: Changes in Body Composition with Age and Mutation Analysis of ALMS1 in 12 United Kingdom Kindreds with Alström Syndrome

Minton, Jayne A.L.; Owen, Katharine R.; Ricketts, Christopher J.; Crabtree, Nicola; Shaikh, Guftar; Ehtisham, Sarah; Porter, J. R.; Carey, Catherine; Hodge, David O.; Paisey, R.; Walker, Mark; Barrett, Timothy

doi:10.1210/jc.2005-2633

Cited by 86 publications

(72 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4 Furthermore, even when carefully matched for pubertal stage and body composition, patients with Alström syndrome are much more severely insulin resistant than controls. 5 One interpretation is that Alström syndrome leads to relative adipose failure without frank lipodystrophy.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of the Alström syndrome-associated gene Alms1 in 3T3-L1 preadipocytes impairs adipogenesis but has no effect on cell-autonomous insulin action

Huang-Doran

Semple

2010

Int J Obes

View full text Add to dashboard Cite

Alström syndrome is a rare genetic syndrome associated with early-onset obesity, severe insulin resistance (IR) that is disproportionate to the degree of adiposity and premature diabetes. The ALMS1 gene, which is mutated in Alström syndrome, encodes a giant 460 kDa centrosome-and basal body-associated protein. Its function is unknown, although roles in primary cilia formation and function, intracellular organelle trafficking and, most recently, adipocyte differentiation have been mooted. We now test the hypothesis that the severe IR and dyslipidaemia in Alström syndrome are accounted for by a partial defect in adipogenesis and/or insulin action in mature adipocytes, leading to relative failure of adipose tissue to discharge its role in metabolic homeostasis. Stable knockdown of Alms1 expression by 480% in 3T3-L1 preadipocytes was associated with impairment of lipid accumulation and at least a twofold reduction in adipocyte gene expression following hormonal induction of adipogenesis. This was accompanied by a commensurate defect in insulin-stimulated glucose uptake. Proximal signalling events in response to insulin were unaffected. These results suggest that partial impairment of adipogenesis in Alström syndrome may contribute to the severity of the associated metabolic phenotype, whereas the ability of insulin to stimulate glucose uptake into adipocytes is grossly unimpaired.

show abstract

Section: Introductionmentioning

confidence: 99%

Knockdown of the Alström syndrome-associated gene Alms1 in 3T3-L1 preadipocytes impairs adipogenesis but has no effect on cell-autonomous insulin action

Huang-Doran

Semple

2010

Int J Obes

View full text Add to dashboard Cite

show abstract

“…With an estimated prevalence of < 1:100 000, only ~500 cases of AS have been reported in the literature thus far. (3,11,13,(17)(18)(19)(20) Since the condition was first described in 1959, (7)(8). The diagnosis of Alström syndrome is based on cardinal clinical features that emerge throughout infancy, childhood, and young adulthood.…”

Section: Discussionmentioning

confidence: 99%

ALSTROM Syndrome (Cases presentation and review of literature)

Al-Kaabi¹

2017

IJPN

View full text Add to dashboard Cite

“…17 Jan.D.Marshall et al, studied 182 cases and described cardiac, pulmonary, neuro-behavioural manifestations included clonic tic and absence seizures, hepatic, urologic, gastrointestinal manifestations of the disease. Dilated cardiomyopathy occurred in 60% of patients in study population.…”

Section: Years To 14 Yearsmentioning

confidence: 99%

Alstrom Syndrome: A Case Report

Shivakumar¹,

Hareesh²,

Rekha³

2015

jemds

View full text Add to dashboard Cite

Alstrom Syndrome was first described by Carl Henry Alstrom in 1959. The key features include childhood onset obesity, congenital retinal dystrophy leading to blindness, sensori-neural deafness. The associated endocrinologic aspects are early onset type 2 Diabetes Mellitus, hyperinsulinemia, hypertriglyceridemia. Mutations in the ALMS1 gene have been found to be causative for AS.The normal protein is present at very low levels in most tissues. The mutation results in a non-functional protein, explaining the various signs and symptoms of Alstrom's. Here we report on a case with Alstrom Syndrome at the age of 28 years. She came with the complaints of generalised swelling of the body, breathlessness, decreased urine output with a significant past history of visual and hearing impairment, diabetes, hypertension, and recurrent urinary tract infections. Awareness of Alstrom Syndrome is lacking despite the complexity and lethality of this disorder. Thus Alstrom Syndrome can be thought of as a rare genetic disorder with several feature similar to metabolic syndrome. It is a rare disease and difficult to make differential diagnosis with other similar syndromes, therefore this case will be a good example of Alstrom Syndrome for the literature.

show abstract

Syndromic Obesity and Diabetes: Changes in Body Composition with Age and Mutation Analysis of ALMS1 in 12 United Kingdom Kindreds with Alström Syndrome

Cited by 86 publications

References 31 publications

Knockdown of the Alström syndrome-associated gene Alms1 in 3T3-L1 preadipocytes impairs adipogenesis but has no effect on cell-autonomous insulin action

Knockdown of the Alström syndrome-associated gene Alms1 in 3T3-L1 preadipocytes impairs adipogenesis but has no effect on cell-autonomous insulin action

ALSTROM Syndrome (Cases presentation and review of literature)

Alstrom Syndrome: A Case Report

Contact Info

Product

Resources

About