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

被引：79

作者：

Ajluni, Nevin ^{[1
,2
]}

Meral, Rasimcan ^{[1
,2
]}

Neidert, Adam H. ^{[1
,2
]}

Brady, Graham F. ^{[3
]}

Buras, Eric ^{[1
,2
]}

McKenna, Barbara ^{[4
]}

DiPaola, Frank ^{[5
]}

Chenevert, Thomas L. ^{[6
]}

Horowitz, Jeffrey F. ^{[7
]}

Buggs-Saxton, Colleen ^{[8
]}

Rupani, Amit R. ^{[9
,10
]}

Thomas, Peedikayil E. ^{[9
,10
]}

Tayeh, Marwan K. ^{[9
,10
]}

Innis, Jeffrey W. ^{[9
,10
]}

Omary, M. Bishr ^{[3
,11
]}

Conjeevaram, Hari ^{[3
]}

Oral, Elif A. ^{[1
,2
]}

机构：

[1] Univ Michigan, Brehm Ctr Diabet Res, 1000 Wall St,Room 5313, Ann Arbor, MI 48105 USA

[2] Univ Michigan, Div Metab Endocrinol & Diabet, 1000 Wall St,Room 5313, Ann Arbor, MI 48105 USA

[3] Univ Michigan, Dept Internal Med, Div Gastroenterol, 1000 Wall St,Room 5313, Ann Arbor, MI 48105 USA

[4] Univ Michigan, Dept Pathol, 1000 Wall St,Room 5313, Ann Arbor, MI 48105 USA

[5] Univ Michigan, Div Pediat Gastroenterol, 1000 Wall St,Room 5313, Ann Arbor, MI 48105 USA

[6] Univ Michigan, Dept Radiol, 1000 Wall St,Room 5313, Ann Arbor, MI 48105 USA

[7] Univ Michigan, Sch Kinesiol, 1000 Wall St,Room 5313, Ann Arbor, MI 48105 USA

[8] Wayne State Univ, Sch Med, Childrens Hosp Michigan, Pediat Endocrinol, Detroit, MI USA

[9] Univ Michigan, Dept Pediat, 1000 Wall St,Room 5313, Ann Arbor, MI 48105 USA

[10] Univ Michigan, Dept Communicable Dis & Human Genet, 1000 Wall St,Room 5313, Ann Arbor, MI 48105 USA

[11] Univ Michigan, Dept Mol & Integrat Physiol, 1000 Wall St,Room 5313, Ann Arbor, MI 48105 USA

来源：

CLINICAL ENDOCRINOLOGY | 2017年 / 86卷 / 05期

基金：

美国国家卫生研究院;

关键词：

FAMILIAL PARTIAL LIPODYSTROPHY; TYPE-2; DIABETES-MELLITUS; FATTY LIVER-DISEASE; DUNNIGAN VARIETY; LAMIN A/C; BODY-COMPOSITION; SCORING SYSTEM; PREVALENCE; MUTATIONS; WOMEN;

D O I：

10.1111/cen.13311

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

ContextPartial lipodystrophy (PL) is associated with metabolic co-morbidities but may go undiagnosed as the disease spectrum is not fully described. ObjectiveThe objective of the study was to define disease spectrum in PL using genetic, clinical (historical, morphometric) and laboratory characteristics. DesignCross-sectional evaluation. ParticipantsTwenty-three patients (22 with familial, one acquired, 78<bold></bold>3% female, aged 12-64 years) with PL and non-alcoholic fatty liver disease (NAFLD). MeasurementsGenetic, clinical and laboratory characteristics, body composition indices, liver fat content by magnetic resonance imaging (MRI), histopathological and immunofluorescence examinations of liver biopsies. ResultsSeven patients displayed heterozygous pathogenic variants in LMNA. Two related patients had a heterozygous, likely pathogenic novel variant of POLD1 (NM002691<bold></bold>3: c.3199 G>A; p.E1067K). Most patients had high ratios (>1<bold></bold>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<bold></bold>3 6<bold></bold>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<bold></bold>3%), hypertension (56<bold></bold>5%) and mood disorders (52<bold></bold>2%) were highly prevalent. Mean NAFLD Activity Score (NAS) was 5 +/- 1 and 78<bold></bold>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. ConclusionsPartial 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.

引用

页码：698 / 707

页数：10

共 38 条

[1]

Efficacy and Safety of Metreleptin in Patients with Partial Lipodystrophy: Lessons from an Expanded Access Program [J].