Clinical Utility Gene Card for: Congenital Generalized Lipodystrophy

Jéru, Isabelle; Vatier, Camille; Araújo‐Vilar, David; Vigouroux, Corinne; Lascols, Olivier

doi:10.1038/ejhg.2016.53

Cited by 5 publications

(7 citation statements)

References 15 publications

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“…Our genetic investigations have recapitulated the genetic heterogeneity of PL with multiple patients having different molecular basis for their disease. Several genes have been implicated in various forms of FPLD including LMNA , PPARG , PLIN1 , AKT2 CIDEC, LIPE and ADR2A . However, the molecular cause of disease remains unexplained in up to 40% of patients.…”

Section: Discussionmentioning

confidence: 99%

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

Ajluni

Meral

Neidert

et al. 2017

Clinical Endocrinology

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Context Partial lipodystrophy (PL) is associated with metabolic co-morbidities but may go undiagnosed as the disease spectrum is not fully described. Objective Define disease spectrum in PL using genetic, clinical (historical, morphometric) and laboratory characteristics. Design Cross-sectional evaluation. Participants 23 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 MRI, histopathological and immunofluorescence examinations of liver biopsies. Results 7 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 %fat trunk to %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 hemoglobin 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) score 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 PL 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.

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Section: Discussionmentioning

confidence: 99%

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

Ajluni

Meral

Neidert

et al. 2017

Clinical Endocrinology

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“…Diagnosis of BSCL is particularly important so that lifestyle interventions can be adopted from an early age to prevent metabolic complications 4,20 . Subsequent treatment of complications can be adapted to meet specific patient needs; and appropriate genetic counselling can be provided 21 . However, some phenotypes are initially less severe than others and diagnosis may be delayed (e.g.…”

Section: Discussionmentioning

confidence: 99%

Monogenic forms of lipodystrophic syndromes: diagnosis, detection, and practical management considerations from clinical cases

Vatier

Vantyghem

Storey

et al. 2018

Current Medical Research and Opinion

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Lipodystrophic syndromes are rare diseases of genetic or acquired origin characterized by partial or generalized lack of body fat. Early detection and diagnosis are crucial to prevent and manage associated metabolic dysfunctions, i.e. insulin resistance, dyslipidemia, fatty liver and diabetes, and to provide appropriate genetic counselling. By means of several representative case studies, this article illustrates the diagnostic and management challenges of lipodystrophic syndromes.Berardinelli-Seip congenital lipodystrophy (BSCL) is typically diagnosed at birth, or soon thereafter, with generalized lipoatrophy and hepatomegaly secondary to hepatic steatosis.Physicians must also consider this diagnosis in adults with atypical non-autoimmune diabetes, hypertriglyceridemia and a lean and muscular phenotype. The BSCL1 subtype due to mutations in the AGPAT2 gene can have an unusual presentation, especially in neonates and infants. Particular attention should be paid to infants presenting failure to thrive who also have hepatomegaly and metabolic derangements. The BSCL2 subtype due to mutations in the BSCL gene tends to be more severe than BSCL1, and is characterized by greater fat loss, mild intellectual disability, earlier onset of diabetes, and higher incidence of premature death.Effective management from an earlier age may moderate the natural disease course.Partial lipodystrophies may easily be confused with common central obesity and/or metabolic syndrome. In patients with unexplained pancreatitis and hypertriglyceridemia, lipodystrophies such as familial partial lipodystrophy type 2 (FPLD2; Dunnigan type, due to LMNA mutations) should be considered. Oral combined contraceptives, which can reveal the disease by inducing severe hypertriglyceridemia, are contraindicated. Endogenous estrogens may also lead to 'unmasking' of the FPLD2 phenotype, which often appears at puberty and is more severe in females than males.Diet and exercise, adapted to age and potential comorbidities, are essential prerequisites for therapeutic management. Metreleptin therapy can be useful to manage lipodystrophy-related metabolic complications.

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“…Se han publicado cerca de 300 casos en el mundo, con una prevalencia aproximada de 1/10.000.000 de habitantes y predominio en las mujeres 1 . Presenta un patrón de herencia autosómica recesiva debido a la mutación de cuatro genes identificados hasta el momento que se han relacionado con subtipos clínicos [2][3][4][5][6] .…”

Section: Comentariosunclassified

“…BSCL3-7q31 codifica la proteína caveolina-1 y se expresa clínicamente con estatura baja. BSCL4-17q21 codifica la proteína cavina-1 y se asocia a debilidad muscular, retraso del desarrollo, anomalías articulares, estenosis pilórica y arritmia cardíaca grave [2][3][4] .…”

Section: Comentariosunclassified

Síndrome de Berardinelli-Seip, un hallazgo dermatológico

et al. 2022

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El síndrome de Berardinelli-Seip es una enfermedad autosómica recesiva poco frecuente (prevalencia mundial de 1/10.000.000 habitantes), que pertenece al grupo de los síndromes con lipodistrofia congénita generalizada. Clínicamente, se caracteriza por la pérdida de tejido adiposo generalizada, hipertrofia del tejido muscular, crecimiento acelerado durante la infancia, pubertad precoz y trastornos lipídicos.Se lo ha clasificado en cuatro variantes con distintos genes implicados que determinan sus características clínicas específicas.Se comunica un caso clásico del síndrome de Berardinelli-Seip, detectado a partir de las manifestaciones dermatológicas, que permite realizar un adecuado diagnóstico y seguimiento multidisciplinario.

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Clinical Utility Gene Card for: Congenital Generalized Lipodystrophy

Cited by 5 publications

References 15 publications

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

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

Monogenic forms of lipodystrophic syndromes: diagnosis, detection, and practical management considerations from clinical cases

Síndrome de Berardinelli-Seip, un hallazgo dermatológico

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