Metabolic and other morbid complications in congenital generalized lipodystrophy type 4

Akinci, Gulcin; Alyaarubi, Saif; Patni, Nivedita; Alhashmi, Nadia; Al‐Shidhani, Azza; Prodam, Flavia; Gagne, Nancy; Babalola, Funmbi; Al Senani, Aisha; Muniraj, Kavitha; Elsayed, Solaf M.; Beghini, Marianna; Saydam, Basak Ozgen; Allawati, Moosa; Vaishnav, Madhumati S.; Can, Ender; Simsir, Ilgin Y.; Sorkina, Ekaterina; Dursun, Fatma; Kamrath, Clemens; Cavdar, Umit; Chakraborty, Partha P.; Dogan, Ozlem Akgun; Al Hosin, Aliya; Al Maimani, Ashwaq; Comunoglu, Nil; Hamed, Ahmed; Huseinbegovic, Tea; Scherer, Thomas; Curtis, Jacqueline; Brown, Rebecca J.; Topaloglu, Haluk; Simha, Vinaya; Wabitsch, Martin; Tuysuz, Beyhan; Oral, Elif A.; Akinci, Baris; Garg, Abhimanyu

doi:10.1002/ajmg.a.63533

Cited by 3 publications

(3 citation statements)

References 34 publications

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“…In addition to the 2016 multi-society lipodystrophy guidelines ( 4 ), the American Diabetes Association (ADA) guideline can be helpful for cardiovascular risk management and hypertension treatment among patients with diabetes ( 27 , 29 ). Patients with subtypes of lipodystrophy syndromes predisposed to cardiomyopathy or arrhythmia should undergo more detailed cardiac evaluation ( 32 , 33 ). This is especially important before initiating an exercise regimen.…”

Section: Resultsmentioning

confidence: 99%

“…It should be noted that patients with LMNA mutations are more likely to develop cardiac disease than others with FPLD ( 33 ). Moreover, certain types of lipodystrophy syndromes (e.g., CGL4) are linked to potentially fatal cardiac rhythm changes and prompt diagnosis is therefore vital to minimize risk of sudden cardiac death ( 31 , 32 ). It is critical to identify and to treat these arrhythmias before they lead to sudden cardiac death.…”

Section: Discussionmentioning

confidence: 99%

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A rapid action plan to improve diagnosis and management of lipodystrophy syndromes

Fourman,

Lima,

Simha

et al. 2024

Front. Endocrinol.

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IntroductionLipodystrophy syndromes are rare diseases that can present with a broad range of symptoms. Delays in diagnosis are common, which in turn, may predispose to the development of severe metabolic complications and end-organ damage. Many patients with lipodystrophy syndromes are only diagnosed after significant metabolic abnormalities arise. Prompt action by clinical teams may improve disease outcomes in lipodystrophy syndromes. The aim of the Rapid Action Plan is to serve as a set of recommendations from experts that can support clinicians with limited experience in lipodystrophy syndromes.MethodsThe Rapid Action Plan was developed using insights gathered through a series of advisory meetings with clinical experts in lipodystrophy syndromes. A skeleton template was used to facilitate interviews. A consensus document was developed, reviewed, and approved by all experts.ResultsLipodystrophy is a clinical diagnosis. The Rapid Action Plan discusses tools that can help diagnose lipodystrophy syndromes. The roles of clinical and family history, physical exam, patient and family member photos, routine blood tests, leptin levels, skinfold measurements, imaging studies, and genetic testing are explored. Additional topics such as communicating the diagnosis to the patients/families and patient referrals are covered. A set of recommendations regarding screening and monitoring for metabolic diseases and end-organ abnormalities is presented. Finally, the treatment of lipodystrophy syndromes is reviewed.DiscussionThe Rapid Action Plan may assist clinical teams with the prompt diagnosis and holistic work-up and management of patients with lipodystrophy syndromes, which may improve outcomes for patients with this rare disease.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A rapid action plan to improve diagnosis and management of lipodystrophy syndromes

Fourman,

Lima,

Simha

et al. 2024

Front. Endocrinol.

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“…There are few studies on bone radiological findings in CGL, apart CGL4 ( 12 ). Most are case reports or series of cases ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity and high prevalence of bone manifestations, and bone mineral density in congenital generalized lipodystrophy subtypes 1 and 2

Freire,

Brasil d’Alva,

Madeira

et al. 2024

Front. Endocrinol.

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IntroductionCongenital Generalized Lipodystrophy (CGL) is a rare autosomal recessive disease caused by mutations in genes responsible for the formation and development of adipocytes. Bone abnormalities are described. However, there is a scarcity of data.ObjectiveTo describe bone characteristics in a large CGL1 and 2 case series.MethodsCross-sectional study that assessed bone radiological features of CGL patients of a reference hospital in Fortaleza (CE), Brazil. Patients underwent clinical and bone mineral metabolism evaluation, radiographs of the axial and appendicular skeleton and bone mineral density (BMD) assessment by DEXA (dual energy X-ray absorptiometry).ResultsNineteen patients were included, fourteen were CGL1 and 5, CGL2. Median age was 20 years (8–42) and 58% were women. Median BMI and percentage of body fat were, respectively, 21 Kg/m² (16–24), and 10.5% (7.6-15). The median leptin concentration was 1 ng/mL (0.1-3.3). Diabetes mellitus and dyslipidemia were present in 79% and 63% of patients, respectively. Median calcium and phosphate were normal in almost all patients (95%). Median parathyroid hormone and 25-OH-vitamin D were 23 pg/mL (7-75) and 28 ng/mL (18-43). Osteolytic lesions, osteosclerosis and pseudo-osteopoikylosis, were present in 74%, 42% and 32% of patients, respectively. Lytic lesions were found predominantly in the extremities of long bones, bilaterally and symmetrically, spine was spared. Osteosclerosis was present in axial and appendicular skeleton. Pseudo-osteopoikilosis was found symmetrically in epiphyses of femur and humerus, in addition to the pelvis. BMD Z-score greater than +2.5 SD was observed in 13 patients (68.4%). BMD was higher in CGL1 compared to CGL2 in lumbar spine and total body in adults. No associations were found between high BMD and HOMA-IR (p=0.686), DM (p=0.750), osteosclerosis (p=0.127) or pseudo-osteopoikilosis (p=0.342), and, between pain and bone lesions. Fractures were found in 3 patients.ConclusionBone manifestations are prevalent, heterogeneous, and silent in CGL1 and CGL2. Osteolytic lesions are the most common, followed by osteosclerosis and pseudo-osteopoikilosis. Bone mass is high in most cases. There was no pain complaint related to bone lesions. Thus, systematic assessment of bone manifestations in CGL is essential. Studies are needed to better understand its pathogenesis and clinical consequences.

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Lipodystrophiesyndrome – klinische Präsentation und Management

Beghini,

Scherer

2024

J. Endokrinol. Diabetol. Stoffw.

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ZusammenfassungLipodystrophien umfassen eine heterogene Gruppe seltener Erkrankungen, die durch einen vollständigen oder partiellen Verlust von Fettgewebe gekennzeichnet sind. Die meisten Formen sind genetisch bedingt, und dazu zählen die kongenitale generalisierte Lipodystrophie (CGL) und die familiäre partielle Lipodystrophie (FPLD).Lipodystrophien sind oft mit schwerer Insulinresistenz, Diabetes mellitus Typ 2, Hypertriglyzeridämie, metabolischer Dysfunktion-assoziierter Fettlebererkrankung (MASLD) und erhöhtem kardiovaskulärem Risiko verbunden, was zu einer erhöhten Morbidität und Mortalität führt. Die klinische Präsentation variiert je nach Form der Lipodystrophie, mit häufigen metabolischen Komplikationen wie Fettlebererkrankung bzw. Fibrose/Zirrhose, Pankreatitis, schwer einstellbarem Diabetes mellitus Typ 2 und kardiovaskulären Erkrankungen bzw. frühzeitigen Ereignissen wie Herzinfarkt und Schlaganfall.Die Diagnose wird klinisch gestellt und basiert auf Anamnese, körperlicher Untersuchung und laborchemischen Untersuchungen, ergänzt durch bildgebende Verfahren zur Quantifizierung des Fettmangels. Gentests können hilfreich sein, negative Ergebnisse schließen aber eine Lipodystrophie prinzipiell nicht aus.Die Behandlung umfasst Lebensstilmodifikationen und die Therapie der Begleiterkrankungen, insbesondere des Diabetes bzw. der Dyslipidämie. Zusätzlich kann das humane rekombinante Leptin-Analogon Metreleptin für die Behandlung der generalisierten Lipodystrophie und in ausgewählten Fällen auch für partielle Lipodystrophie eingesetzt werden. Eine multidisziplinäre Betreuung in spezialisierten Zentren ist aufgrund der Komplexität und Vielfalt der möglichen Komplikationen entscheidend.

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Metabolic and other morbid complications in congenital generalized lipodystrophy type 4

Cited by 3 publications

References 34 publications

A rapid action plan to improve diagnosis and management of lipodystrophy syndromes

A rapid action plan to improve diagnosis and management of lipodystrophy syndromes

Heterogeneity and high prevalence of bone manifestations, and bone mineral density in congenital generalized lipodystrophy subtypes 1 and 2

Lipodystrophiesyndrome – klinische Präsentation und Management

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