scholarly journals Metreleptin as A Rescue Therapy in A Patient With A Novel Mutation for Familial Partial Lipodystrophy Type 3, Originally Presenting as Type 1 Diabetes.

2021 ◽  
Author(s):  
VAIA LAMBADIARI ◽  
AIKATERINI KOUNTOURI ◽  
EIRINI MARATOU ◽  
STAVROS LIATIS ◽  
GEORGE DIMITRIADIS ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Effective Treatment ◽  
Novel Mutation ◽  
Genetic Disorder ◽  
Synthetic Analogue ◽  
Metabolic Complications ◽  
Partial Lipodystrophy ◽  
Familial Partial Lipodystrophy ◽  
Type 3

Abstract Background: Familial partial lipodystrophy type 3 (FPLD3) is a very rare autosomal dominant genetic disorder which is caused by mutations in the peroxisome proliferator activated receptor gamma (PPARG) gene. It is characterized by a partial loss of adipose tissue leading to subnormal leptin secretion and metabolic complications. Metreleptin, a synthetic analogue of human leptin, is an effective treatment for generalized lipodystrophies, but the evidence for efficacy in patients with FPLD3 is scarce. Case presentation: We present a 61-year-old woman, initially misdiagnosed as type 1 diabetes since the age of 29, with severe insulin resistance, who gradually displayed a more generalized form of lipoatrophy and extreme hypertriglyceridemia, hypertension and multiple manifestations of cardiovascular disease. She was found to carry a novel mutation leading to PPARGGlu157Gly variant. After six months of metreleptin treatment HbA1c decreased from 10% to 7.9% and fasting plasma triglycerides were dramatically reduced from 2.919 mg/dl to 198 mg/dl. Conclusions: This case highlights the importance of early recognition of FPLD syndromes otherwise frequently observed as a difficult-to-classify and manage diabetes cases, in order to prevent cardiovascular complications. Metreleptin may be an effective treatment for FPLD3.

scholarly journals Case Report: Metreleptin Treatment in a Patient With a Novel Mutation for Familial Partial Lipodystrophy Type 3, Presenting With Uncontrolled Diabetes and Insulin Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Vaia Lambadiari ◽  
Aikaterini Kountouri ◽  
Eirini Maratou ◽  
Stavros Liatis ◽  
George D. Dimitriadis ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Effective Treatment ◽  
Early Recognition ◽  
Novel Mutation ◽  
Genetic Disorder ◽  
Synthetic Analogue ◽  
Metabolic Complications ◽  
Partial Lipodystrophy ◽  
Familial Partial Lipodystrophy ◽  
Type 3

BackgroundFamilial partial lipodystrophy type 3 (FPLD3) is a very rare autosomal dominant genetic disorder which is caused by mutations in the peroxisome proliferator activated receptor gamma (PPARG) gene. It is characterized by a partial loss of adipose tissue leading to subnormal leptin secretion and metabolic complications. Metreleptin, a synthetic analogue of human leptin, is an effective treatment for generalized lipodystrophies, but the evidence for efficacy in patients with FPLD3 is scarce.Case PresentationWe present a 61-year-old woman, initially misdiagnosed as type 1 diabetes since the age of 29, with severe insulin resistance, who gradually displayed a more generalized form of lipoatrophy and extreme hypertriglyceridemia, hypertension and multiple manifestations of cardiovascular disease. She was found to carry a novel mutation leading to PPARGGlu157Gly variant. After six months of metreleptin treatment, HbA1c decreased from 10 to 7.9% and fasting plasma triglycerides were dramatically reduced from 2.919 mg/dl to 198 mg/dl.ConclusionsThis case highlights the importance of early recognition of FPLD syndromes otherwise frequently observed as difficult-to-classify and manages diabetes cases, in order to prevent cardiovascular complications. Metreleptin may be an effective treatment for FPLD3.

scholarly journals Challenges in Managing Metabolic Complications in a Patient With Familial Partial Lipodystrophy Type 3

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A307-A308
Author(s):  
Kajal Shah ◽  
Marina Charitou
Keyword(s):  
Insulin Resistance ◽  
Subcutaneous Fat ◽  
Peroxisome Proliferator ◽  
Metabolic Complications ◽  
Peroxisome Proliferator Activated Receptor ◽  
Partial Lipodystrophy ◽  
Familial Partial Lipodystrophy ◽  
Type 3 ◽  
Pparγ Gene

Abstract Familial partial lipodystrophy (FPL) is a rare group of autosomal dominant genetic disorders which causes variable loss of subcutaneous fat from abdomen, thorax or extremities in addition to the numerous metabolic complications like insulin resistance, diabetes mellitus and dyslipidemia1. FPL type 3 was first characterized by Agarwal et al. in 20021, in which peroxisome proliferator-activated receptor-γ (PPARγ) gene was the molecular basis of this disorder. It is extremely rare and so far only 30 patients or so have been recognized with this mutation2. FPL3 is unique because it generally spares the loss of fat from trunk, face and neck region and also presents with more severe metabolic derangements. We report a case of a young female with PPARγ mutation leading to numerous metabolic complications. A 19 year old female with FPL3 was seen by adult endocrinology as a transition from pediatric endocrinology. She was found to have hypertriglyceridemia on routine labs done at the age of 11. Patient reported loss of subcutaneous fat from her extremities and eruptive xanthoma on flexor surfaces at the time of diagnosis along with a positive family history of hypertriglyceridemia induced pancreatitis and Myocardial infarction at the age of 40 in her father. Her triglyceride level has varied between 600 and 3000 (normal 20–149 mg/dl) over the years. FPL3 was diagnosed based on genetic testing. She was prescribed fenofibrate and fish oil, and statin was added thereafter. She developed type 2 diabetes and was started on metformin and pioglitazone. She was noted to have hypertension and was treated with amlodipine and lisinopril. She also was found to have Polycystic Ovarian Syndrome (PCOS) based on menstrual irregularities, hirsutism and ultrasound showing multiple ovarian cysts, and was treated with spironolactone. Her most recent labs show triglyceride level of 2400 mg/dl and HbA1c of 8.3. PPARγ gene mutation in FPL3 leads to insulin resistance and hence patients often develop hypertriglyceridemia, type 2 diabetes, PCOS and hypertension. In terms of treatment options, we are still limited to pioglitazone, metformin, statins and fish oil. Often these are not sufficient in addressing the complexity of metabolic derangements in these patients who have an increased risk of cardiovascular events at a young age. Further research about agents targeting this gene in particular would be beneficial. 1. Agarwal et al. A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familial partial lipodystrophy. J Clin Endocrinol Metab. 2002 Jan; 87(1):408–411. 2. Garg A. Lipodystrophies: Genetic and Acquired Body Fat Disorders. J Clin Endocrinol Metab. 2011;96(11): 3313–3325.

scholarly journals Gaucher's Disease - A case report

2015 ◽  
Vol 2 (2) ◽  
pp. 130
Author(s):  
Preeti Bajaj ◽  
Jyoti Kasture ◽  
Balbir Singh Shah
Keyword(s):  
Autosomal Recessive ◽  
Genetic Disorder ◽  
Early Adulthood ◽  
Lysosomal Storage ◽  
Gaucher's Disease ◽  
Gaucher’S Disease ◽  
Type 3 ◽  
Storage Disorders

Gaucher's Disease (GD) is an autosomal recessive systemic lysosomal storage disorder which is characterized by glucocerebroside deposition in cells of the macrophage-monocyte system as a result of a deficiency in lysosomal P-glycosidase (glucocerebrosidase). GD is a rare genetic disorder. It is the most common amongst the lysosomal storage disorders. GD has been categorised into three types based on the presence of central nervous involvement1. Type 1 is a non-neuronopathic form that presents in childhood or early adulthood. Type 2 is acute neuronopathic form that presents in childhood. It progresses rapidly and is fatal. Type 3 is chronic non-neuronopathic form that presents in childhood but is slowly progressive. Here we describe a case of a three and a half year old male child in whom a diagnosis of Gaucher's disease was made based on bone marrow biopsy and later confirmed by glucocerebrosidase levels estimation.

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.

scholarly journals Recovery from alopecia areata in a patient with autoimmune polyglandular syndrome type 3

2015 ◽  
Vol 2015 ◽  
Author(s):  
Shinya Makino ◽  
Takeshi Uchihashi ◽  
Yasuo Kataoka ◽  
Masayoshi Fujiwara
Keyword(s):  
Type 1 Diabetes ◽  
Alopecia Areata ◽  
Human Leukocyte ◽  
Diabetic Patients ◽  
List Type ◽  
Human Leukocyte Antigen Typing ◽  
Autoimmune Polyglandular Syndrome ◽  
Autoimmune Polyglandular Syndrome Type ◽  
Type 3

Summary Recovery from alopecia is rare in autoimmune polyglandular syndrome (APS). A 41-year-old male was admitted to our hospital with hyperglycemia. He developed alopecia areata (AA) 5 months before admission and developed thirst, polyuria, and anorexia in 2 weeks. His plasma glucose level upon admission was 912 mg/dl (50.63 mmol/l) and HbA1c was 13.7%. Although urinary and plasma C-peptide levels showed that insulin secretion was not depleted, anti-insulinoma-associated antigen 2 antibody was present. In addition, measurement of thyroid autoantibodies revealed the presence of Hashimoto's thyroiditis. These findings suggested a diagnosis of APS type 3. The patient has showed signs of improvement with the continuation of insulin therapy. During the successful control of diabetes, he had total hair regrowth within 2–3 months. Human leukocyte antigen typing showed that DRB1*1501-DQB1*0602 and DQB1*0301 were present. Similar cases should be accumulated to clarify the association of APS type 3 with recovery from AA. Learning points Alopecia in diabetic patients is a suspicious manifestation of autoimmune type 1 diabetes. Patients with autoimmune type 1 diabetes specifically manifesting alopecia should be further examined for diagnosis of APS. Insulin-mediated metabolic improvement may be a factor, but not the sole factor, determining a favorable outcome of alopecia in patients with autoimmune type 1 diabetes.

scholarly journals Familial partial lipodystrophy type 3: a new mutation on the PPARG gene

HORMONES ◽  
2015 ◽  
pp. 317-320 ◽  
Author(s):  
Eva Lau ◽  
Davide Carvalho ◽  
Joana Oliveira ◽  
Susana Fernandes ◽  
Paula Freitas
Keyword(s):  
New Mutation ◽  
Partial Lipodystrophy ◽  
Familial Partial Lipodystrophy ◽  
Pparg Gene ◽  
Type 3
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