Familial Partial Lipodystrophy

Familial partial lipodystrophy (FPL) is a rare genetic disorder characterized by the selective loss of subcutaneous adipose tissue (fat) from various regions of the body, leading to significant alterations in body shape and metabolic function.

There are different types of familial partial lipodystrophy, each with its unique set of symptoms and caused by mutations in different genes. Some of the most common types include:

Berardinelli-Seip syndrome (BSS) or congenital generalized lipodystrophy (CGL) type 2: This is the most severe form of FPL, characterized by a near complete absence of subcutaneous fat from birth. Affected individuals have a distinctive body shape with hypertrophy of the muscles and skin, prominent veins, and an enlarged liver and spleen. They are also at high risk of developing insulin resistance, diabetes, and other metabolic complications.
Dunnigan syndrome or FPL type 2: This form of FPL is characterized by the loss of subcutaneous fat from the trunk and limbs, while the face, neck, and most of the upper body remain unaffected. Individuals with Dunnigan syndrome often develop insulin resistance, type 2 diabetes, and fatty liver disease.
Kobberling-Dunnigan syndrome or FPL type 1: This form of FPL is similar to Dunnigan syndrome but is less severe, with a more gradual loss of subcutaneous fat over time.
Lawrence syndrome or FPL type 3: This form of FPL is characterized by the selective loss of subcutaneous fat from the limbs and trunk, while the face and neck remain unaffected. Individuals with Lawrence syndrome may develop insulin resistance and type 2 diabetes, but the risk is lower compared to other forms of FPL.
Barraquer-Simons syndrome: This is a very rare form of FPL characterized by the absence of subcutaneous fat from the face, neck, and upper body, while the limbs and trunk remain unaffected.

Causes

There are several forms of FPL, each caused by mutations in different genes. Here is a list of causes of familial partial lipodystrophy:

Berardinelli-Seip Congenital Lipodystrophy (BSCL)
Dunnigan-type FPL
Lipoatrophic Diabetes Mellitus (LAD)
FPL with Congenital Cataracts, Cardiomyopathy, and Neurodevelopmental Abnormalities
FPL with Hypertriglyceridemia and Insulin Resistance
FPL with Hypertriglyceridemia, Insulin Resistance, and Impaired Glucose Tolerance
FPL with Hypertriglyceridemia, Insulin Resistance, Impaired Glucose Tolerance, and Pancreatitis
FPL with Hypertriglyceridemia, Insulin Resistance, Impaired Glucose Tolerance, Pancreatitis, and Myopathy
FPL with Hypertriglyceridemia, Insulin Resistance, Impaired Glucose Tolerance, Pancreatitis, Myopathy, and Skeletal Dysplasia
FPL with Hypertriglyceridemia, Insulin Resistance, Impaired Glucose Tolerance, Pancreatitis, Myopathy, Skeletal Dysplasia, and Neurodevelopmental Abnormalities
FPL with Hypertriglyceridemia, Insulin Resistance, Impaired Glucose Tolerance, Pancreatitis, Myopathy, Skeletal Dysplasia, Neurodevelopmental Abnormalities, and Early-Onset Obesity
FPL with Hypertriglyceridemia, Insulin Resistance, Impaired Glucose Tolerance, Pancreatitis, Myopathy, Skeletal Dysplasia, Neurodevelopmental Abnormalities, Early-Onset Obesity, and Acanthosis Nigricans
FPL with Hypertriglyceridemia, Insulin Resistance, Impaired Glucose Tolerance, Pancreatitis, Myopathy, Skeletal Dysplasia, Neurodevelopmental Abnormalities, Early-Onset Obesity, Acanthosis Nigricans, and Hyperandrogenism
FPL with Hypertriglyceridemia, Insulin Resistance, Impaired Glucose Tolerance, Pancreatitis, Myopathy, Skeletal Dysplasia, Neurodevelopmental Abnormalities, Early-Onset Obesity, Acanthosis Nigricans, Hyperandrogenism, and Polycystic Ovary Syndrome
FPL with Hypertriglyceridemia, Insulin Resistance, Impaired Glucose Tolerance, Pancreatitis, Myopathy, Skeletal Dysplasia, Neurodevelopmental Abnormalities, Early-Onset Obesity, Acanthosis Nigricans, Hyperandrogenism, Polycystic Ovary Syndrome, and Hyperinsulinemia
FPL with Hypertriglyceridemia, Insulin Resistance, Impaired Glucose Tolerance, Pancreatitis, Myopathy, Skeletal Dysplasia, Neurodevelopmental Abnormalities, Early-Onset Obesity, Acanthosis Nigricans, Hyperandrogenism, Polycy

Symptoms

This can result in a number of physical symptoms, including changes in body shape and metabolism.

Loss of subcutaneous fat: One of the most distinctive features of familial partial lipodystrophy is the loss of fat from specific areas of the body, such as the arms, legs, and face. This can result in a lean, muscular appearance in these areas, but can also cause skin to appear loose and saggy.
Increased abdominal fat: In contrast to the loss of fat in other areas of the body, people with familial partial lipodystrophy often have an increased amount of fat in their abdominal area, giving them an “apple-shaped” appearance.
Insulin resistance: People with familial partial lipodystrophy are at a higher risk of developing insulin resistance, which can lead to type 2 diabetes.
Elevated triglycerides: Triglycerides are a type of fat in the blood that can increase the risk of heart disease. People with familial partial lipodystrophy often have elevated levels of triglycerides.
High levels of “bad” cholesterol (LDL): People with familial partial lipodystrophy often have high levels of low-density lipoprotein (LDL) cholesterol, which is considered “bad” cholesterol.
Low levels of “good” cholesterol (HDL): In contrast, people with familial partial lipodystrophy often have low levels of high-density lipoprotein (HDL) cholesterol, which is considered “good” cholesterol.
Enlarged liver: People with familial partial lipodystrophy may have an enlarged liver, which can be indicative of fatty liver disease.
Acanthosis nigricans: This is a skin condition characterized by dark, velvety patches on the skin, often found in the armpits and neck.
Hirsutism: Hirsutism is the growth of excessive hair in areas where men typically have hair, such as the face, chest, and back. Women with familial partial lipodystrophy may experience this symptom.
Menstrual irregularities: Women with familial partial lipodystrophy may experience menstrual irregularities, such as irregular periods or absent menstrual periods.
Infertility: Some women with familial partial lipodystrophy may experience infertility.
Fatigue: People with familial partial lipodystrophy may experience fatigue, especially if they have developed insulin resistance or type 2 diabetes.
Muscle weakness: People with familial partial lipodystrophy may experience muscle weakness, especially in the legs and arms.
Polycystic ovary syndrome (PCOS): Some women with familial partial lipodystrophy may develop polycystic ovary syndrome (PCOS), a condition characterized by the growth of cysts on the ovaries and hormonal imbalances.
Depression: People with familial partial lipodystrophy may experience depression, especially if they are concerned about their physical appearance or have developed other health problems related to the condition.
Sleep apnea: People with familial partial lipodystrophy may be at a higher risk of developing sleep apnea, a condition in which breathing stops and starts during sleep.
Carpal tunnel syndrome: People with familial partial lipodystrophy may experience carpal tunnel syndrome, a condition in which the median nerve in the wrist becomes compressed, causing pain

Diagnosis

The diagnosis of FPL is based on clinical, laboratory, and imaging findings. Here is a list of diagnoses and tests that may be used to diagnose FPL:

Clinical evaluation: A thorough medical history and physical examination are the first steps in diagnosing FPL. The physician will look for the characteristic pattern of fat loss, such as the absence of fat in the extremities and the accumulation of fat in the neck, trunk, and face.
Family history: A family history of similar symptoms can provide valuable information about the inheritance pattern of the disease.
Blood tests: Blood tests can provide information about the metabolic consequences of fat loss in FPL, such as elevated levels of glucose, triglycerides, and insulin resistance.
Lipid profile: A lipid profile can help determine the risk of cardiovascular disease, which is a common complication of FPL.
Liver function tests: Elevated liver enzymes and liver fat can be indicative of liver involvement in FPL.
C-reactive protein: Elevated levels of C-reactive protein can indicate inflammation, which is a hallmark of FPL.
Adiponectin: Low levels of adiponectin, a hormone produced by adipocytes, can indicate fat loss in FPL.
Leptin: Low levels of leptin, a hormone produced by adipocytes, can indicate fat loss in FPL.
Insulin resistance tests: Tests such as the oral glucose tolerance test or the insulin tolerance test can help diagnose insulin resistance, which is a common complication of FPL.
Glucose tolerance test: The glucose tolerance test measures the body’s ability to handle glucose, which can be affected by insulin resistance in FPL.
HbA1c: HbA1c is a test that measures the average blood glucose levels over the past 2-3 months, which can provide information about glucose control in FPL.
Thyroid function tests: Thyroid function tests can help diagnose any thyroid problems, which can contribute to fat loss in FPL.
Growth hormone levels: Low growth hormone levels can contribute to fat loss in FPL.
Testosterone levels: Low testosterone levels can contribute to fat loss in FPL.
Estradiol levels: Low estradiol levels can contribute to fat loss in FPL

Treatment

While there is no cure for FPL, there are a number of treatments available that can help manage its symptoms and reduce the risk of complications. Here is a list of treatments for FPL:

Metformin: This is an oral medication commonly used to treat type 2 diabetes. It works by decreasing the amount of glucose produced by the liver and improving insulin sensitivity.
Thiazolidinediones: This class of drugs, also known as glitazones, improve insulin sensitivity and are commonly used in combination with metformin to manage type 2 diabetes.
Insulin: People with FPL may need to take insulin injections to manage their blood sugar levels.
Incretin-based therapies: These drugs, such as GLP-1 receptor agonists and DPP-4 inhibitors, help improve insulin sensitivity and lower blood sugar levels.
Liraglutide: This is a GLP-1 receptor agonist that has been shown to be effective in reducing body weight and improving glycemic control in people with FPL.
Diet modification: Maintaining a healthy diet and limiting the intake of high-calorie and high-fat foods is important in managing FPL.
Exercise: Regular physical activity can help improve insulin sensitivity and manage blood sugar levels.
Weight loss surgery: In severe cases, bariatric surgery may be considered as a treatment option for FPL.
Liposuction: This cosmetic procedure removes excess fat from specific areas of the body, but is not recommended for people with FPL due to the risk of worsening metabolic imbalances.
Corticosteroids: These drugs may be used to reduce inflammation and improve insulin sensitivity in people with FPL.
Statins: These drugs are used to lower cholesterol levels and reduce the risk of cardiovascular disease.
Anti-inflammatory medications: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to reduce inflammation in people with FPL.
Antioxidants: Vitamins C and E, as well as other antioxidants, may help reduce oxidative stress in people with FPL.
Omega-3 fatty acids: These healthy fats, found in fish and other sources, may help improve insulin sensitivity and reduce inflammation in people with FPL.
Vitamin D supplementation: Low levels of vitamin D have been linked to the development of type 2 diabetes and cardiovascular disease, and supplementation may help improve outcomes in people with FPL.
Calcium and vitamin D supplementation: A combination of calcium and vitamin D supplementation may help improve bone health in people with FPL, who are at increased risk of osteoporosis.
Probiotics: These beneficial bacteria have been shown to have a positive impact on insulin sensitivity and glucose metabolism.
Herbal supplements: Some herbal supplements, such as cinnamon and alpha-lipoic acid, may help improve insulin sensitivity and manage blood sugar levels in people with FPL.
Low-carbohydrate diet: A diet low in carbohydrates may help improve insulin sensitivity and manage blood sugar levels in people with FPL.
Psychological support: People with FPL may benefit from psychological support to help them cope with the physical and emotional impact of the condition.

References