Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Familial Partial Lipodystrophy

What is Familial Partial Lipodystrophy?

• Familial Partial Lipodystrophy (FPL), also known as Kobberling-Dunnigan Syndrome, is characterized by progressive, selective body fat loss in the body​
• FPL can affect an individual in a variety of ways, which can include reduced ability to break down glucose, raised levels of triglycerides in the blood, and diabetes​
• The estimated incidence rate for FPL is around 1 in 1,000,000 people in the general population, although misdiagnoses/undiagnoses may skew that number​​
• Diagnosis of FPL is based upon observation and identification of characteristic symptoms, in combination with some clinical tests to aid in the diagnosis, and/or rule out other possible diseases​
• The type of tissue lost due to FPL cannot be reversed, so addressing symptoms early and consistent monitoring may help patients avoid major complications in the future ​

How Do You Get It?

• The majority of individuals who have been reported to have the disease in published medical literature have been European, although individuals of African and Asian-Indian decent have also been reported to have the disease​
• Given how this disease affects patients’ appearance, cosmetic surgery may add additional economic strains on top of the medical costs for treating the disease​
• Sex​
  • FPL is reported more often in women, but this may be caused by women being affected by the disease more severely, meaning it is recognized more often​
• Age Onset​
  • Age of onset usually starts around puberty, when an affected individual starts loosing fat, although some types of FPL don’t have symptoms appearing until a person’s 20s
• Genetic Factors​
  • There are four types of FPL that have been linked to autosomal dominant traits which are inherited, although there is a type that is inherited via an autosomal recessive trait​
• Hereditary Factors​
  • The risk of passing on the abnormal gene for the dominant genetic types of FPL is 50%, regardless of the sex of the child​
  • The chance of passing on the recessive genetic type of FPL is 25%, although the chance of the child being a carrier is 50%​
• White people seem to be at higher risk than other racial groups

What Are The Symptoms?

• In most cases, an individual with FPL usually has symptoms first appearing during puberty, with progressive loss of subcutaneous fat​
• Symptoms can get worse over time if they go untreated for too long​
• Symptoms can vary by the type of FPL that an individual has. These types include:
• FPL Type 1​ (Kobberling Variety)​
  • Similar to the symptoms of Type 2, but fat loss is generally confined to just the arms and legs. Other symptoms include: insulin resistance, high blood pressure, and hypertriglyceridemia (Type 2 has only been reported in women)​
• FPL Type 2​ (Dunnigan Variety)​
  • Most common form. Symptoms include: fat loss during puberty in arms, legs, and abdomen (more so in the buttocks and hips for women), fat accumulation in other areas of the body, insulin resistance, acanthosis nigricans, enlarged liver, and cirrhosis​
• FPL Type 3​ (PPARG Mutation)​
  • This type of FPL has only been reported in about 30 people. It is milder than FPL Type 2, but symptoms can include: Fat loss prominently in the calves, upper arms, and thighs, diabetes, hypertriglyceridemia, hypertension, fatty liver, and pancreatitis ​
• FPL Type 4​ (PLIN1 Mutation)​
  • This type of FPL has only been reported in a few individuals. Symptoms can include: lipodystrophy with a concentration on the lower limbs and buttocks, muscular hypertrophy in the calves, insulin resistance, severe hypertriglyceridemia, and diabetes​
• FPL Type 5​ (AKT2 Mutation)​
  • This type of FPL has only been reported in four members of the same family. Symptoms included: hypertension, severe insulin resistance, diabetes mellitus, and lipodystrophy mostly in the arms and legs​
• FPL Type 6​ (CIDEC Mutation)​
  • This type of FPL is also known as Autosomal Recessive FPL and has only one reported case in medical literature. Their symptoms were: partial lipodystrophy, severe insulin resistance, fatty liver, acanthosis nigricans, and diabetes​

How Is It Treated?

• Treatment of FPL is currently confined towards the individual symptoms of the disease, as there is no currently approved treatment to address the disease as a whole.
• The goal of treatment is to address each symptom independently​
• Treatment administration method and duration varies by the co-morbidity that is being treated. These can vary from high-dose insulin injections to a pacemaker ​
• Barriers to treatment include going undiagnosed/misdiagnosed and symptoms remaining hidden until problematic (not continually monitoring the effects of the disease) ​
• The treatment team for an individual may require coordinated efforts of a number of different specialists, such as a surgeon, cardiologist, endocrinologist, nutritionist, and possibly a pediatrician, depending on the age of the affected person​
• Treatment and the prognosis of FPL depend on two major factors: the type of FPL a person has, and the severity of the co-morbidities associated with the disease​
• Co-morbidity Treatments​
  • Psychosocial​
    • Therapy, support, and counseling may help an affected individual and their families cope​
  • Diabetes​
    • Insulin may be provided, sometimes in high-doses​
  • Cardiovascular disease​
    • Periodic heart evaluations can help detect problems early on, and those affected with CVD may require use of a pacemaker​
  • Hypertriglyceridemia​
    • Fibric acid derivatives, statins, or n-3 polysaturated fatty acids can help those with severe hypertriglyceridemia​
  • Lipodystrophy​
    • Plastic/cosmetic surgery may help those who have had their appearance altered or fat accumulations ​
  • Hypertension​
    • Anti-hypertensive drugs may be used to treat high blood pressure​
• Diet & Exercise
  • Although clinical trial evidence is lacking, there is a major push for those affected with FPL to follow a high carbohydrate, low-fat diet, although caution must be taken around low density lipoprotein triglyceride build up​
  • Regular exercise is also encouraged as a means to decrease the chances of developing some co-morbidities, such as diabetes and fat accumulation​
• Co-morbidities that can affect prognosis of the disease include:​
  • Cardiovascular disease​
  • Diabetes​
  • Pancreatitis​
  • Fatty/enlarged liver​

Where Can I Learn More???

• Check out our cornerstone on this disease here.
• Learn more about this disease from the National Organization for Rare Disorders.