Summary about Disease
Familial partial lipodystrophy (FPLD) is a group of rare genetic disorders characterized by selective loss of subcutaneous adipose tissue (fat) from specific areas of the body, typically the limbs and trunk, while fat may accumulate in other areas, such as the face, neck, and intra-abdominal region. This altered fat distribution can lead to insulin resistance, diabetes, hypertriglyceridemia (high levels of triglycerides in the blood), and other metabolic complications. Several subtypes of FPLD exist, each associated with specific gene mutations and varying degrees of fat loss and metabolic abnormalities.
Symptoms
Symptoms of FPLD vary depending on the specific subtype and the individual's genetic makeup. Common symptoms include:
Selective fat loss: Primarily from the limbs (arms and legs) and trunk (abdomen and buttocks). This loss is usually progressive and becomes noticeable during late childhood or adolescence.
Muscle prominence: Due to the loss of subcutaneous fat, muscles may appear more defined than normal.
Increased fat deposition in other areas: Often the face, neck (leading to a "cushingoid" appearance), and intra-abdominal area (visceral fat).
Insulin resistance: A key feature that can lead to glucose intolerance, pre-diabetes, or type 2 diabetes.
Hypertriglyceridemia: Elevated levels of triglycerides in the blood.
Low HDL cholesterol: Decreased levels of "good" cholesterol.
Acanthosis nigricans: Dark, velvety patches of skin, typically in skin folds like the neck and armpits, indicating insulin resistance.
Polycystic ovary syndrome (PCOS) in women: Can cause irregular periods, hirsutism (excessive hair growth), and infertility.
Liver abnormalities: Including fatty liver disease (non-alcoholic fatty liver disease or NAFLD) and, in rare cases, cirrhosis.
Cardiovascular disease: Increased risk due to metabolic abnormalities.
Causes
FPLD is caused by genetic mutations that affect the development, differentiation, or function of adipocytes (fat cells). The most common genes implicated include:
_LMNA_: (FPLD2) Mutations in the _LMNA_ gene, which encodes lamin A/C, a protein essential for nuclear structure and function, are the most frequent cause of FPLD.
_PPARgamma_: (FPLD3) Mutations in the _PPARgamma_ gene, which encodes a transcription factor crucial for adipocyte differentiation and lipid metabolism, are less common.
_AKT2_: (FPLD5) Mutations in the _AKT2_ gene are rare and have been associated with lipodystrophy and insulin resistance.
_PLIN1_: (FPLD4) Mutations in the _PLIN1_ gene are associated with partial lipodystrophy with severe insulin resistance These mutations are typically inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene is sufficient to cause the disorder. However, some cases may arise from spontaneous mutations.
Medicine Used
Treatment for FPLD focuses on managing the metabolic complications and addressing individual symptoms. There is no cure for the underlying genetic defect. Medications used may include:
Insulin-sensitizing agents: Metformin and thiazolidinediones (e.g., pioglitazone) to improve insulin sensitivity and manage diabetes.
Insulin: For individuals with diabetes who require insulin therapy.
Lipid-lowering agents: Statins, fibrates, or omega-3 fatty acids to manage hypertriglyceridemia and reduce the risk of cardiovascular disease.
Metreleptin: Recombinant human leptin analog. FDA-approved for treating metabolic complications of generalized lipodystrophy, but may also be used off-label for some patients with certain subtypes of partial lipodystrophy. Important note: Metreleptin requires REMS program due to the risks.
Medications for PCOS: Oral contraceptives, anti-androgens, or fertility treatments for women with PCOS.
Other medications: To manage specific complications such as liver abnormalities or cardiovascular disease.
Is Communicable
No, familial partial lipodystrophy is not communicable. It is a genetic disorder caused by inherited or spontaneous gene mutations and cannot be spread from person to person through any means.
Precautions
Precautions for individuals with FPLD mainly revolve around managing and monitoring the metabolic complications associated with the condition. These precautions include:
Regular medical check-ups: To monitor blood glucose levels, lipid profiles, liver function, and cardiovascular health.
Adherence to prescribed medications: Taking medications as directed to manage diabetes, hypertriglyceridemia, and other metabolic abnormalities.
Healthy lifestyle: Following a balanced diet that is low in saturated fat and simple sugars, and engaging in regular physical activity to improve insulin sensitivity and maintain a healthy weight.
Monitoring for complications: Being vigilant for signs and symptoms of diabetes, cardiovascular disease, liver disease, and other complications, and seeking prompt medical attention if they occur.
Genetic counseling: For individuals with FPLD and their families, to understand the inheritance pattern and the risk of passing the condition on to future generations.
How long does an outbreak last?
FPLD is not an "outbreak" situation, since it is a genetic condition. The symptoms are progressive, and they persist throughout life without treatment. With treatments symptoms can be maintained.
How is it diagnosed?
Diagnosis of FPLD typically involves a combination of:
Clinical evaluation: Assessing the patient's physical appearance, including the distribution of fat and the presence of acanthosis nigricans or other associated features.
Medical history: Reviewing the patient's personal and family history of lipodystrophy, diabetes, hyperlipidemia, and other metabolic disorders.
Laboratory tests: Measuring blood glucose levels, lipid profiles (triglycerides, cholesterol), liver function tests, and insulin levels.
Imaging studies: Such as MRI or CT scans, to assess the distribution of fat in different parts of the body.
Genetic testing: To identify mutations in genes known to cause FPLD, such as _LMNA_, _PPARgamma_, _AKT2_, and _PLIN1_. Genetic testing can confirm the diagnosis and help determine the specific subtype of FPLD.
Timeline of Symptoms
The onset and progression of symptoms in FPLD can vary depending on the specific subtype and individual factors. A general timeline might look like this:
Childhood/Adolescence:
Subcutaneous fat loss typically becomes noticeable, often starting in the limbs and trunk.
Muscle prominence becomes apparent.
Insulin resistance may begin to develop, potentially leading to acanthosis nigricans.
Adulthood:
Metabolic complications such as diabetes, hypertriglyceridemia, and low HDL cholesterol become more prevalent.
Women may develop PCOS.
Liver abnormalities, such as fatty liver disease, may develop.
Increased risk of cardiovascular disease.
The progression of fat loss and redistribution may continue. It is important to note that this is a general timeline and the specific course of the disease can vary considerably.
Important Considerations
Early diagnosis is crucial: Early diagnosis and management can help prevent or delay the onset of serious metabolic complications.
Personalized treatment: Treatment should be tailored to the individual's specific symptoms and needs, focusing on managing metabolic abnormalities and preventing complications.
Psychological support: The physical changes associated with FPLD can have a significant impact on self-esteem and body image, and psychological support may be beneficial.
Family screening: Family members of individuals with FPLD may benefit from genetic screening to identify those at risk of developing the condition.
Research: Ongoing research is essential to improve our understanding of FPLD and develop new and more effective treatments.
Multidisciplinary care: Management of FPLD often requires a multidisciplinary approach, involving endocrinologists, geneticists, cardiologists, hepatologists, and other specialists.