New Metabolic Phenotypes in Laminopathies:<i>LMNA</i>Mutations in Patients with Severe Metabolic Syndrome

Decaudain, A.; Vantyghem, Marie-Christine; Guerci, Bruno; Hécart, A.C.; Auclair, Martine; Reznik, Yves; Narbonne, H.; Ducluzeau, Pierre-Henri; Donadille, Bruno; Lebbe, Célèste; Béréziat, Véronique; Capeau, Jacqueline; Lascols, Olivier; Vigouroux, Corinne

doi:10.1210/jc.2007-0654

Cited by 139 publications

(111 citation statements)

References 43 publications

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“…In FPLD2, SAT is lost around the time of puberty from the legs, arms, buttocks, abdomen and chest; areas of remaining SAT deposits are on the back, face and chin, giving a Cushingoid appearance; fat is increased in the labia majora in women [24] ; this finding also occurs in women with MSL ( Figure 1). Mutations in the lamin A and C gene, LMNA, cause FPLD2 [25] . People with FPLD2 have all the co-morbidities associated with obesity.…”

Section: Familial Partial Lipodystrophies (Fpld)mentioning

confidence: 99%

Rare adipose disorders (RADs) masquerading as obesity

2012

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Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidencebased data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations.

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Section: Familial Partial Lipodystrophies (Fpld)mentioning

confidence: 99%

Rare adipose disorders (RADs) masquerading as obesity

2012

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“…Among the lipodystrophies, LMNA mutations have been reported most frequently in patients with familial partial lipodystrophy (FPLD) of the Dunnigan variety, an autosomal dominant condition characterized by gradual loss of adipose tissue from the extremities and trunk starting at the puberty. However, phenotypic heterogeneity in the pattern of body fat loss has been observed among the laminopathies (11,12,13,14,15,16,17). Therefore, in this study, we searched for LMNA mutations in patients with various forms of lipodystrophy.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations

Mory

Crispim

Freire

et al. 2012

European Journal of Endocrinology

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Objective: Mutations in LMNA have been linked to diverse disorders called laminopathies, which display heterogeneous phenotypes and include diseases affecting muscles, axonal neurons, progeroid syndromes, and lipodystrophies. Among the lipodystrophies, LMNA mutations have been reported most frequently in patients with familial partial lipodystrophy (FPLD) of the Dunnigan variety; however, phenotypic heterogeneity in the pattern of body fat loss has been observed. In this study, we searched for LMNA mutations in patients with various forms of lipodystrophy. Design and methods: We studied 21 unrelated individuals with lipodystrophy. Subjects underwent a complete clinical evaluation and were classified as typical FPLD (nZ12), atypical partial lipodystrophy (nZ7), or generalized lipodystrophy (nZ2). Molecular analysis of LMNA gene, analysis of body fat by dual-energy X-ray absorptiometry, and biochemical measurements were performed.

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“…Metabolic alterations such as insulin resistance, hypertriglyceridemia and liver steatosis are characteristics of lipodystrophies. Recent studies describe new phenotypes of metabolic laminopathies, even in the absence of obvious clinical lipoatrophy (22) or associated with premature ageing process (14).…”

Section: Discussionmentioning

confidence: 99%

Atypical generalized lipoatrophy and severe insulin resistance due to a heterozygous LMNA p.T10I mutation

Mory

Crispim

Kasamatsu

et al. 2008

Arq Bras Endocrinol Metab

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Lipodystrophies are a group of heterogeneous disorders characterized by the loss of adipose tissue and metabolic complications. The main familial forms of lipodystrophy are Congenital Generalized Lipodystrophy and Familial Partial Lipodystrophy (FPLD). FPLD may result from mutations in the LMNA gene. Besides FPLD, mutations in LMNA have been shown to be responsible for other inherited diseases called laminopathies. Here we describe the case of a 15-year-old girl who was referred to our service due to diabetes mellitus and severe hypertriglyceridemia. Physical examination revealed generalized loss of subcutaneous fat, confi rmed by DEXA (total body fat 8.6%). As the patient presented with pubertal-onset of generalized lipodystrophy and insulin resistance, molecular analysis of the LMNA gene was performed. We identifi ed a heterozygous substitution in exon 1 (c.29C>T) predicting a p.T10I mutation. In summary, we describe an atypical phenotype of lipodistrophy associated with a de novo appearance of the p.

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New Metabolic Phenotypes in Laminopathies:LMNAMutations in Patients with Severe Metabolic Syndrome

Cited by 139 publications

References 43 publications

Rare adipose disorders (RADs) masquerading as obesity

Rare adipose disorders (RADs) masquerading as obesity

Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations

Atypical generalized lipoatrophy and severe insulin resistance due to a heterozygous LMNA p.T10I mutation

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