scholarly journals MON-695 Multiple Recurrent Lipomatoses with Thiazolidinedione Therapy in Familial Partial Lipodystrophy, Dunnigan Variety (FPLD2)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nivedita Patni ◽  
Abhimanyu Garg
Keyword(s):  
White Female ◽  
Missense Mutations ◽  
Autosomal Dominant Disorder ◽  
Metabolic Complications ◽  
Partial Lipodystrophy ◽  
Lmna Mutation ◽  
Gradual Loss ◽  
History Of ◽  
Familial Partial Lipodystrophy ◽  
One Year

Abstract Background: FPLD2, a rare autosomal dominant disorder due to heterozygous missense mutations in LMNA, is characterized by gradual loss of subcutaneous (sc) fat from the limbs starting during late childhood and predisposition to metabolic complications, such as diabetes, dyslipidemia and hepatic steatosis. Some patients, especially females, accumulate excess sc fat in the chin, neck, supraclavicular and perineal regions. We report disfiguring and disabling lipomatoses in unusual locations with thiazolidinedione therapy in two women with FPLD2. Clinical Cases: A 57-year-old white female with FPLD2, due to heterozygous p.R482Q LMNA mutation, developed recurrent large lipomatoses in the axillae at age 33 years, and later in the posterior neck (buffalo hump), mons pubis and above sacrum. She developed diabetes at age 30 and was started on pioglitazone 45 mg daily, which was switched to rosiglitazone 8 mg daily at age 43 years. Supra-sacral lipomatoses were approximately 40 cm X 20 cm bilaterally and continued to grow despite lipectomy and multiple liposuctions. Rosiglitazone was stopped at age 56 years, and she reported no further increase in the size of lipomatoses. Her other medications included colesevelam, atorvastatin, metformin, glimepiride, lisinopril, losartan, hydrochlorothiazide, aspirin, insulin and dulaglutide. Her 54-year-old younger sister with FPLD2 (heterozygous p.R482Q LMNA mutation) was treated with lisinopril, metoprolol, atorvastatin, liraglutide, and insulin glargine and aspart, but no history of taking thiazolidinediones, and she never developed any lipomatoses. Another 43-year-old white female with FPLD2, due to heterozygous p.S583L LMNA mutation, was noticed to have lipomatous deposits in the axillae, medial gluteal region, labia and perineal regions. She developed diabetes mellitus at age 36 years and took metformin for 6 years and pioglitazone 30 mg daily for one year before she noticed the lipomatoses. Her other medications included atorvastatin, aldactone and vitamin D3. Pioglitazone was stopped and after one year, she reported reduction in the size of lipomatoses. Conclusion: Thiazolidinediones are selective peroxisomal proliferator-activated receptor-γ agonists and induce weight gain by increasing fat mass, especially subcutaneous depots. Our cases suggest that thiazolidinediones can cause undesired growth of non-lipodystrophic adipose tissue in patients with FPLD2 and thus should be avoided.

scholarly journals Diagnostic Value of Anthropometric Measurements for Familial Partial Lipodystrophy, Dunnigan Variety

2020 ◽  
Vol 105 (7) ◽  
pp. 2132-2141
Author(s):  
Chandna Vasandani ◽  
Xilong Li ◽  
Hilal Sekizkardes ◽  
Beverley Adams-Huet ◽  
Rebecca J Brown ◽  
...  
Keyword(s):  
Lower Limb ◽  
False Negative ◽  
Skinfold Thickness ◽  
Diagnostic Value ◽  
Small Sample ◽  
Anthropometric Measurements ◽  
Metabolic Complications ◽  
Partial Lipodystrophy ◽  
Adult Females ◽  
Familial Partial Lipodystrophy

Abstract Context Familial partial lipodystrophy, Dunnigan variety (FPLD2) is a rare autosomal dominant disorder resulting from LMNA causal variants, which is characterized by loss of subcutaneous fat from the extremities and predisposition to metabolic complications. The diagnostic value of various anthropometric measurements for FPLD2 remains unknown. Objective To determine specificity and sensitivity of anthropometric measurements for the diagnosis of FPLD2. Methods We measured skinfold thickness and regional body fat by dual energy X-ray absorptiometry (DXA) in 50 adult females and 6 males with FPLD2 at UT Southwestern and compared their data with the sex- and age-matched controls from the National Health and Nutrition Examination Survey (NHANES) 1999-2010. We further compared data from 1652 unaffected females from the Dallas Heart Study and 23 females with FPLD2 from the National Institutes of Health with the NHANES data. Results The DXA-derived lower limb fat (%) had the best specificity (0.995) and sensitivity (1.0) compared with the upper limb fat, truncal fat, the ratio of lower limb to truncal fat, and triceps skinfold thickness for adult females with FPLD2. The lower limb fat below 1st percentile of NHANES females had a false-positive rate of 0.0054 and a false negative rate of 0. The diagnostic value of anthropometric parameters could not be determined for males with FPLD2 due to small sample size. Conclusions The lower limb fat (%) is the best objective anthropometric measure for diagnosing FPLD2 in females. Women with below the 1st percentile lower limb fat should undergo genetic testing for FPLD2, especially if they have metabolic complications.

Familial partial lipodystrophy associated with the heterozygous LMNA mutation 1445G>A (Arg482Gln) in a Polish family

2010 ◽  
Vol 44 (3) ◽  
pp. 291-296 ◽  
Author(s):  
Hanna Drac ◽  
Agnieszka Madej-Pilarczyk ◽  
Krystyna Gospodarczyk-Szot ◽  
Małgorzata Gaweł ◽  
Hubert Kwieciński ◽  
...  
Keyword(s):  
Partial Lipodystrophy ◽  
Lmna Mutation ◽  
Familial Partial Lipodystrophy

A case of familial partial lipodystrophy caused by a novel lamin A/C (LMNA) mutation in exon 1 (D47N)

2016 ◽  
Vol 29 ◽  
pp. 37-39 ◽  
Author(s):  
Nilufer Ozdemir Kutbay ◽  
Banu Sarer Yurekli ◽  
Huseyin Onay ◽  
Canan Tuncer Altay ◽  
Tahir Atik ◽  
...  
Keyword(s):  
Lamin A ◽  
Partial Lipodystrophy ◽  
Lmna Mutation ◽  
Exon 1 ◽  
Familial Partial Lipodystrophy

scholarly journals Heterogeneity of Nuclear Lamin A Mutations in Dunnigan-Type Familial Partial Lipodystrophy*

2000 ◽  
Vol 85 (9) ◽  
pp. 3431-3435
Author(s):  
Robert A. Hegele ◽  
Henian Cao ◽  
Carol M. Anderson ◽  
Irene M. Hramiak
Keyword(s):  
Environmental Factors ◽  
Novel Mutation ◽  
Compound Heterozygote ◽  
Lamin A ◽  
Missense Mutations ◽  
Compound Heterozygosity ◽  
Partial Lipodystrophy ◽  
Nuclear Lamin ◽  
Familial Partial Lipodystrophy ◽  
Affected Subject

Abstract We previously identified a novel mutation, namely LMNA R482Q, that was found to underlie Dunnigan-type partial lipodystrophy (FPLD) and diabetes in an extended Canadian kindred. We have since sequenced LMNA in five additional Canadian FPLD probands and herein report three new rare missense mutations in LMNA: V440M, R482W, and R584H. One severely affected subject was a compound heterozygote for both V440M and R482Q. The findings indicated that 1) a spectrum of LMNA mutations underlies FPLD; 2) aberrant lamin A, and not lamin C, is likely to underlie FPLD, as R584H occurs within LMNA sequence that is specific for lamin A; 3) the V440M mutation may not cause lipodystrophy on its own; 4) compound heterozygosity for V440M and R482Q is associated with a relatively more severe FPLD phenotype, but not with complete lipodystrophy; and 5) variation in the severity of the phenotype might be related to environmental factors.

scholarly journals Case Report: An Atypical Form of Familial Partial Lipodystrophy Type 2 Due to Mutation in the Rod Domain of Lamin A/C

2021 ◽  
Vol 12 ◽  
Author(s):  
Carolina Cecchetti ◽  
M. Rosaria D’Apice ◽  
Elena Morini ◽  
Giuseppe Novelli ◽  
Carmine Pizzi ◽  
...  
Keyword(s):  
Genetic Diagnosis ◽  
Coiled Coil ◽  
Missense Variant ◽  
Lamin A ◽  
Metabolic Complications ◽  
Partial Lipodystrophy ◽  
Atypical Form ◽  
Amino Terminal ◽  
Familial Partial Lipodystrophy

PurposeFamilial partial lipodystrophy type 2 (FPLD2) patients generally develop a wide variety of severe metabolic complications. However, they are not usually affected by primary cardiomyopathy and conduction system disturbances, although a few cases of FPLD2 and cardiomyopathy have been reported in the literature. These were all due to amino-terminal heterozygous lamin A/C mutations, which are considered as new forms of overlapping syndromes.Methods and ResultsHere we report the identification of a female patient with FPLD2 due to a heterozygous missense variant c.604G>A in the exon 3 of the LMNA gene, leading to amino acid substitution (p.Glu202Lys) in the central alpha-helical rod domain of lamin A/C with a high propensity to form coiled-coil dimers. The patient’s cardiac evaluations that followed the genetic diagnosis revealed cardiac rhythm disturbances which were promptly treated pharmacologically.ConclusionsThis report supports the idea that there are “atypical forms” of FPLD2 with cardiomyopathy, especially when a pathogenic variant affects the lamin A/C head or alpha-helical rod domain. It also highlights how increased understanding of the genotype-phenotype correlation could help clinicians to schedule personalized monitoring of the lipodystrophic patient, in order to prevent uncommon but possible devastating manifestations, including arrhythmias and sudden death.

scholarly journals Diagnostic Challenge in PLIN1-Associated Familial Partial Lipodystrophy

2019 ◽  
Vol 104 (12) ◽  
pp. 6025-6032 ◽  
Author(s):  
Isabelle Jéru ◽  
Marie-Christine Vantyghem ◽  
Elise Bismuth ◽  
Pascale Cervera ◽  
Sara Barraud ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary ◽  
Liver Steatosis ◽  
Subcutaneous Fat ◽  
Diagnostic Challenge ◽  
Metabolic Complications ◽  
Partial Lipodystrophy ◽  
Patients With Diabetes ◽  
Familial Partial Lipodystrophy ◽  
Center For Rare Diseases

Abstract Context Heterozygous frameshift variants in PLIN1 encoding perilipin-1, a key protein for lipid droplet formation and triglyceride metabolism, have been implicated in familial partial lipodystrophy type 4 (FPLD4), a rare entity with only six families reported worldwide. The pathogenicity of other PLIN1 null variants identified in patients with diabetes and/or hyperinsulinemia was recently questioned because of the absence of lipodystrophy in these individuals and the elevated frequency of PLIN1 null variants in the general population. Objectives To reevaluate the pathogenicity of PLIN1 frameshift variants owing to new data obtained in the largest series of patients with FPLD4. Methods We performed histological and molecular studies for patients referred to our French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity for lipodystrophy and/or insulin resistance and carrying PLIN1 frameshift variants. Results We identified two heterozygous PLIN1 frameshift variants segregating with the phenotype in nine patients from four unrelated families. The FPLD4 stereotypical signs included postpubertal partial lipoatrophy of variable severity, muscular hypertrophy, acromegaloid features, polycystic ovary syndrome and/or hirsutism, metabolic complications (e.g., hypertriglyceridemia, liver steatosis, insulin resistance, diabetes), and disorganized subcutaneous fat lobules with fibrosis and macrophage infiltration. Conclusions These data suggest that some FPLD4-associated PLIN1 variants are deleterious. Thus, the evidence for the pathogenicity of each variant ought to be carefully considered before genetic counseling, especially given the importance of an early diagnosis for optimal disease management. Thus, we recommend detailed familial investigation, adipose tissue-focused examination, and follow-up of metabolic evolution.

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