Unusual Presentations of LMNA-Associated Lipodystrophy with Complex Phenotypes and Generalized Fat Loss: When the Genetic Diagnosis Uncovers Novel Features

Natalia Xavier S. de Andrade, MD; Suleyman Cem Adiyaman, MD; Bernamir De Yuksel, MD; Carla T. Ferrari, MD; Abdelwahab Jalal Eldin, MD; Basak Ozgen Saydam, MD; Canan Altay, MD; Pratima Sharma, MD; Nicole Bhave, MD; Ann Little, MD; Paul McKeever, MD, PhD; Huseyin Onay, MD; Sermin Ozkal, MD; Mustafa Secil, MD; Mustafa Nuri Yenerel, MD; Baris Akinci, MD; Elif A. Oral, MD

AACE Clinical Case Reports (Mar 2020)

Unusual Presentations of LMNA-Associated Lipodystrophy with Complex Phenotypes and Generalized Fat Loss: When the Genetic Diagnosis Uncovers Novel Features

Natalia Xavier S. de Andrade, MD,
Suleyman Cem Adiyaman, MD,
Bernamir De Yuksel, MD,
Carla T. Ferrari, MD,
Abdelwahab Jalal Eldin, MD,
Basak Ozgen Saydam, MD,
Canan Altay, MD,
Pratima Sharma, MD,
Nicole Bhave, MD,
Ann Little, MD,
Paul McKeever, MD, PhD,
Huseyin Onay, MD,
Sermin Ozkal, MD,
Mustafa Secil, MD,
Mustafa Nuri Yenerel, MD,
Baris Akinci, MD,
Elif A. Oral, MD

Affiliations

Natalia Xavier S. de Andrade, MD: From the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan; Division of Endocrinology and Metabolism, Department of Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
Suleyman Cem Adiyaman, MD: Division of Endocrinology and Metabolism, Department of Internal Medicine, Dokuz Eylül University, Izmir, Turkey
Bernamir De Yuksel, MD: Department of Internal Medicine, Dokuz Eylül University, Izmir, Turkey
Carla T. Ferrari, MD: From the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan; Division of Endocrinology and Metabolism, Department of Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
Abdelwahab Jalal Eldin, MD: From the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan
Basak Ozgen Saydam, MD: Division of Endocrinology and Metabolism, Department of Internal Medicine, Dokuz Eylül University, Izmir, Turkey
Canan Altay, MD: Department of Radiology, Dokuz Eylül University, Izmir, Turkey
Pratima Sharma, MD: Division of Gastrointestinal Diseases, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan
Nicole Bhave, MD: Division of Cardiovascular Medicine, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI
Ann Little, MD: Neurology Department, Michigan Medicine, University of Michigan, Ann Arbor, MI
Paul McKeever, MD, PhD: Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI
Huseyin Onay, MD: Department of Medical Genetics, Ege University, Izmir, Turkey
Sermin Ozkal, MD: Department of Pathology, Dokuz Eylül University, Izmir, Turkey
Mustafa Secil, MD: Department of Radiology, Dokuz Eylül University, Izmir, Turkey
Mustafa Nuri Yenerel, MD: Division of Hematology, Department of Internal Medicine, Istanbul University, Istanbul, Turkey.
Baris Akinci, MD: From the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Dokuz Eylül University, Izmir, Turkey
Elif A. Oral, MD: From the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan; Address correspondence to Dr. Elif A. Oral, Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, University of Michigan, 1000 Wall Street, Room 5313, Ann Arbor, MI 48105.

Journal volume & issue: Vol. 6, no. 2
pp. e79 – e85

Abstract

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ABSTRACT: Objective: Lipodystrophy represents a group of rare diseases characterized by loss of body fat. While patients with generalized lipodystrophy exhibit near-total lack of fat, partial lipodystrophy is associated with selective fat loss affecting certain parts of the body. Although classical familial partial lipodystrophy (FPLD) is a well-described entity, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants. Methods: We have encountered 2 unique cases with complex phenotypes, generalized fat loss, and very low leptin levels that made the distinction between generalized versus partial lipodystrophy quite challenging. Results: We present a 61-year-old female with generalized fat loss, harboring the heterozygous pathogenic variant p.R541P (c.1622G>C) on the LMNA gene. The discovery of the pathogenic variant led to correct clinical diagnosis of her muscle disease, identification of significant heart disease, and a recommendation for the implantation of a defibrillator. She was able to start metreleptin based on her generalized fat loss pattern and demonstration of the genetic variant. Secondly, we report a 40-year-old Turkish female with generalized fat loss associated with a novel heterozygous LMNA pathogenic variant p.K486E (c.1456A>G), who developed systemic B cell follicular lymphoma. Conclusion: Clinicians need to recognize that the presence of an LMNA variant does not universally lead to FPLD type 2, but may lead to a phenotype that is more complex and may resemble more closely generalized lipo-dystrophy. Additionally, providers should recognize the multisystem features of laminopathies and should screen for these features in affected patients, especially if the variant is not at the known hotspot for FPLD type 2.

Published in AACE Clinical Case Reports

ISSN: 2376-0605 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the endocrine glands. Clinical endocrinology
Website: https://www.journals.elsevier.com/aace-clinical-case-reports

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