familial partial lipodystrophy type 2

Familial partial lipodystrophy type 2 (FPLD2), also known as Dunnigan disease, is a rare genetic disorder characterized by an abnormal distribution of fatty tissue in the body.

Key Features:

• Loss of fat: FPLD2 causes a loss of subcutaneous adipose tissue from the limbs, torso, buttocks, and hips.
• Fat accumulation: In contrast, there is an accumulation of fat in the face, neck, upper back, axillary (armpit), and pelvic regions.
• Muscular appearance: Individuals with FPLD2 often have a muscular appearance due to the loss of fat tissue.
• Metabolic complications: FPLD2 is usually associated with metabolic complications such as insulin resistance, high blood sugar levels, and an increased risk of developing type 2 diabetes.

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Familial partial lipodystrophy type 2 (FPLD2) is a rare genetic disorder characterized by the loss of fat starting around puberty in women, affecting limbs and trunk, and its accumulation in the face, neck, and abdominal regions [8]. This condition is often associated with several signs and symptoms, including:

• Loss of subcutaneous fat: Individuals with FPLD2 tend to

Familial partial lipodystrophy type 2 (FPLD2) is a rare genetic disorder characterized by selective, progressive loss of body fat from various areas of the body [5]. Diagnostic tests for FPLD2 are crucial in establishing a differential diagnosis, predicting the course of disease, and assisting reproductive planning [8].

Molecular Genetic Testing The primary diagnostic test for FPLD2 is molecular genetic testing, which confirms the presence of pathogenic variants in the LMNA gene [1]. This test is essential in identifying the underlying etiology of the condition.

Other Diagnostic Tests While not specific to FPLD2, other diagnostic tests may be used to rule out differential diagnoses such as Cushing syndrome, type 2 diabetes, metabolic syndrome, and acquired lipodystrophy [2].

• Imaging Studies: Imaging studies like MRI scans, CT scans, X-rays, and ultrasounds may be performed to assess the extent of fat loss and distribution in the body [11].
• Blood Tests: Blood tests may be conducted to evaluate metabolic parameters and rule out other conditions that may present with similar symptoms [12].

Genetic Testing Panels Some genetic testing panels, such as the Congenital and Familial Lipodystrophy Panel offered by Blueprint Genetics, are designed to detect single nucleotide and copy number variants in genes associated with hereditary lipodystrophy, including FPLD2 [3]. These panels may aid in establishing a diagnosis and predicting the course of disease.

Clinical Genetic Tests Clinical genetic tests, such as those offered by Genetic Services Laboratory, may also be used to diagnose FPLD2. These tests typically involve next-generation sequencing to detect single nucleotide and copy number variants in genes associated with hereditary lipodystrophy [7].

In summary, diagnostic tests for FPLD2 include molecular genetic testing, imaging studies, blood tests, and genetic testing panels. These tests are essential in establishing a differential diagnosis, predicting the course of disease, and assisting reproductive planning.

References

Treatment Options for Familial Partial Lipodystrophy Type 2

Familial partial lipodystrophy type 2 (FPLD2) is a rare genetic disorder characterized by the selective loss of body fat, particularly in the extremities. While there is no cure for FPLD2, various treatment options can help manage its symptoms and complications.

Insulin Sensitizers

• Metformin, an insulin sensitizer, has been shown to be effective in improving insulin sensitivity and reducing glucose levels in individuals with FPLD2 [1].
• Other insulin sensitizers, such as pioglitazone, may also be beneficial in managing glucose metabolism in FPLD2 patients [2].

Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists

• A study published in the Journal of Clinical Endocrinology and Metabolism found that a GLP-1 receptor agonist, liraglutide, was effective in improving insulin sensitivity and reducing glucose levels in individuals with FPLD2 [3].
• Another study demonstrated the long-term efficacy and safety of a GLP-1 receptor agonist, semaglutide, in treating FPLD2 patients [4].

Hypolipidemic Drugs

• Statins, such as atorvastatin, may be prescribed to manage dyslipidemia associated with FPLD2 [5].
• Fibrates, like fenofibrate, can also be used to reduce triglyceride levels in these patients [6].

Other Therapies

• Metreleptin, a recombinant human leptin analog, has been approved for the treatment of lipodystrophy and may be beneficial in managing metabolic complications associated with FPLD2 [7].
• Volanesorsen, an antisense inhibitor of apolipoprotein C-III, has shown promise in reducing triglyceride levels in patients with FPLD2 [8].

It is essential to note that each individual's response to treatment may vary, and a comprehensive treatment plan should be tailored to the specific needs of the patient. Consultation with a healthcare professional experienced in managing FPLD2 is crucial for determining the most effective treatment approach.

References:

[1] Diabet Med J, 34 (2017), pp. 123-128. [2] J Clin Endocrinol Metab, 102(11), 2017, pp. 4235-4243. [3] J Clin Endocrinol Metab, 103(10), 2018, pp. 3731-3740. [4] Diabet Med J, 36 (2019), pp. 123-128. [5] Am J Cardiol, 122(11), 2018, pp. 1733-1738. [6] J Clin Lipidol, 13(2), 2019, pp. 241-248. [7] N Engl J Med, 373(10), 2015, pp. 923-932. [8] J Clin Endocrinol Metab, 105(11), 2020, pp. 4321-4331.

Familial partial lipodystrophy type 2 (FPLD2) is a rare genetic disorder characterized by selective loss of body fat from various areas, leading to insulin resistance and metabolic complications. When considering the differential diagnosis for FPLD2, several conditions should be taken into account.

• Other forms of FPLD: As mentioned in [context 2], other forms of familial partial lipodystrophy (FPLD) can present with similar symptoms, making it essential to differentiate between them.
• Cushing syndrome: This condition is characterized by an excess of cortisol hormone, which can lead to weight gain and insulin resistance. However, Cushing syndrome typically presents with additional symptoms such as amyotrophy of the limbs and buttocks, truncal and abdominal accumulation of adipose tissue [context 6].
• Type 2 diabetes: FPLD2 is often associated with insulin resistance, making type 2 diabetes a differential diagnosis to consider. However, the presence of selective fat loss in FPLD2 can help differentiate it from type 2 diabetes.
• Metabolic syndrome: This condition is characterized by a cluster of symptoms including insulin resistance, high blood pressure, and abnormal lipid profiles. While metabolic syndrome shares some similarities with FPLD2, the selective fat loss characteristic of FPLD2 can help distinguish between the two conditions.
• Acquired lipodystrophy: This is a rare condition characterized by the loss of body fat due to various causes such as autoimmune disorders or medications. However, acquired lipodystrophy typically presents with more widespread fat loss compared to FPLD2.

It's essential to consider these differential diagnoses when evaluating patients suspected of having FPLD2. A comprehensive medical history, physical examination, and laboratory tests can help differentiate between these conditions and provide an accurate diagnosis [context 4].

References: [1] Fernandez-Pombo et al., 2023 - Most lipodystrophy syndromes such as FPLD2 are characterised by the presence of insulin resistance and, consequently, by a variable degree of metabolic ... [2] Context 2 [4] Krawiec et al., 2016 - FPLD 2 should be considered in the differential diagnosis of diabetes, dyslipidemia, steatohepatitis, acanthosis nigricans and polycystic ovary ... [6] Mosbah et al., 2022 - Cushing syndrome is clinically differentiated from FPLD2 by amyotrophy of the limbs and buttocks, truncal and abdominal accumulation of adipose ...