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Clin Endocrinol (Oxf). 2017 May;86(5):698-707. doi: 10.1111/cen.13311. Epub 2017 Mar 27.

Spectrum of disease associated with partial lipodystrophy: lessons from a trial cohort.

Author information

1
Brehm Center for Diabetes Research and Division of Metabolism, Endocrinology & Diabetes, University of Michigan, Ann Arbor, MI, USA.
2
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
3
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
4
Division of Pediatric Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
5
Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
6
School of Kinesiology, University of Michigan, Ann Arbor, MI, USA.
7
Pediatric Endocrinology, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI, USA.
8
Departments of Pediatrics and Communicable Diseases and Human Genetics, University of Michigan, Ann Arbor, MI, USA.
9
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.

Abstract

CONTEXT:

Partial lipodystrophy (PL) is associated with metabolic co-morbidities but may go undiagnosed as the disease spectrum is not fully described.

OBJECTIVE:

The objective of the study was to define disease spectrum in PL using genetic, clinical (historical, morphometric) and laboratory characteristics.

DESIGN:

Cross-sectional evaluation.

PARTICIPANTS:

Twenty-three patients (22 with familial, one acquired, 78·3% female, aged 12-64 years) with PL and non-alcoholic fatty liver disease (NAFLD).

MEASUREMENTS:

Genetic, clinical and laboratory characteristics, body composition indices, liver fat content by magnetic resonance imaging (MRI), histopathological and immunofluorescence examinations of liver biopsies.

RESULTS:

Seven patients displayed heterozygous pathogenic variants in LMNA. Two related patients had a heterozygous, likely pathogenic novel variant of POLD1 (NM002691·3: c.3199 G>A; p.E1067K). Most patients had high ratios (>1·5) of percentage fat trunk to percentage fat legs (FMR) when compared to reference normals. Liver fat quantified using MR Dixon method was high (11·3 ± 6·3%) and correlated positively with haemoglobin A1c and triglycerides while leg fat by dual-energy X-ray absorptiometry (DEXA) correlated negatively with triglycerides. In addition to known metabolic comorbidities; chronic pain (78·3%), hypertension (56·5%) and mood disorders (52·2%) were highly prevalent. Mean NAFLD Activity Score (NAS) was 5 ± 1 and 78·3% had fibrosis. LMNA-immunofluorescence staining from select patients (including one with the novel POLD1 variant) showed a high degree of nuclear atypia and disorganization.

CONCLUSIONS:

Partial lipodystrophy is a complex multi-system disorder. Metabolic parameters correlate negatively with extremity fat and positively with liver fat. DEXA-based FMR may prove useful as a diagnostic tool. Nuclear disorganization and atypia may be a common biomarker even in the absence of pathogenic variants in LMNA.

PMID:
28199729
PMCID:
PMC5395301
DOI:
10.1111/cen.13311
[Indexed for MEDLINE]
Free PMC Article

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