There are two main types of FPLD [2]:

• Type I - Loss of fat in the extremities and normal or increased distribution of adipose tissue on the head and neck area, as well as the trunk.
• Type II - Seen only in a few cases, this type is distinguished by loss of fat from both the trunk and the extremities, with marked accumulation in the head and neck region.

Metabolic impairments, primarily in the form of diabetes mellitus, but also hirsutism and dysmenorrhea in women, typically starts during early years of life [3].

• Asymptomatic

  Membranoproliferative glomerulonephritis usually presents with asymptomatic proteinuria or hematuria. The disease may gradually progress. About 40-50% of patients develop end-stage renal disease over the course of 10 years. [emedicine.medscape.com]

  Prepubertal children were asymptomatic, which is consistent with the widely accepted pubertal or postpubertal appearance of the first clinical signs in FPLD. [academic.oup.com]

• Vomiting

  High triglyceride levels can sometimes cause pancreatitis, an inflammation of the pancreas that can cause severe abdominal pain and vomiting. There are multiple types of acquired lipodystrophy. [chop.edu]

  Pancreatitis can be associated with abdominal pain, chills, jaundice, weakness, sweating, vomiting, and weight loss. [rarediseases.org]

• Hypertension

  More than half the men without phenotypic features of FPLD had either IGT/DM, dyslipidemia, hypertension or cardiovascular disease. [ncbi.nlm.nih.gov]

  Size of the problem Causes of hypertension in diabetes Screening for hypertension in diabetes Diagnosis of hypertension in diabetes Investigation of hypertension in diabetes Management of hypertension in diabetes Special considerations in ethnic groups [books.google.com]

• Heart Disease

  For the last twenty years, there has been a growing recognition worldwide of the importance of managing dyslipidemia for the primary and secondary prevention of atherosclerotic vascular disease, especially coronary heart disease. [books.google.com]

  Dr Schmidt correctly states that LMNA mutations do not directly produce atherosclerosis; carriers with coronary heart disease (CHD) end points had hyperinsulinemia, dyslipidemia, hypertension, and diabetes. 3 These intermediate metabolic traits—all potent [circ.ahajournals.org]

  There is an increased risk of coronary heart disease. Cardiomyopathy and muscular dystrophy may occur rarely. Xanthoma and nail changes may occur. Type 3 is due to mutations in the PPARG gene. It is rare with approximately 30 cases reported to date. [en.wikipedia.org]

• Large Hand

  Continued Adults with CGL have large hands and feet and a strong, square jawbone because their hormone balance is off and they keep growing. They could have larger than usual sex organs (clitoris, or penis and testicles). [webmd.com]

• Hirsutism

  She also had hirsutism. Anthropometry and whole body magnetic resonance imaging revealed marked loss of sc fat particularly from the extremities but sc truncal fat was slightly increased. [ncbi.nlm.nih.gov]

  There was a moderate hirsutism (15 points on the Ferrimann-Galwey scale) but no clitoromegaly. [journals.viamedica.pl]

• Absence of Subcutaneous Fat

  Absence of subcutaneous fat from the upper and lower extremities during childhood or puberty. The trunk, arms and legs are affected by fat loss while the neck and face have more than normal fat deposits. [manbironline.com]

  Thin wrinkles of skin under the buttocks confirm the absence of subcutaneous fat. Extremities often appear muscular with visible veins ( Fig. 1 C ) or thin without obvious veins. [doi.org]

• Xanthoma

  Variable symptoms may comprise pancreatitis and/or eruptive xanthomas due to severe hypertriglyceridemia, acanthosis nigricans, polycystic ovaria, and carpal tunnel syndrome. [ncbi.nlm.nih.gov]

  Xanthoma and nail changes may occur. Type 3 is due to mutations in the PPARG gene. It is rare with approximately 30 cases reported to date. It is similar to type 2 but tends to be milder. Type 4 is due to mutations in the PLIN1 gene. [en.wikipedia.org]

  Eruptive xanthoma (0.6%), diabetic foot (0.2%), diabetic bulla (0.4%), diabetic dermopathy (0.2%), generalized granuloma annulare (0.2%), and insulin reactions (6.2%) and lipodystrophy (14%) were also seen. [e-ijd.org]

  Variable symptoms may comprise pancreatitis and/or eruptive xanthomas due to severe hypertriglyceridemia, acanthosis nigricans and polycystic ovaria. [1] Mutations within the lamin A/C (LMNA) gene on chromosome 1q21.2 were recently reported to result [ijem.in]

• Hypertrichosis

  It results in gigantism ( acromegaly ), enlarged liver and kidneys, pancreatitis, acanthosis nigricans and increased body hair (hypertrichosis) as well as generalised loss of body fat. [dermnetnz.org]

  […] cramps Insulin-resistant diabetes mellitus Lipodystrophy Skeletal: Brachydactyly; Supernumerary teeth; Bitemporal skull narrowing GU: Female virilization with clitoromegaly; polycystic ovaries; Sponge kidneys Other: Acanthosis nigricans; Exophthalmos; Hypertrichosis [neuromuscular.wustl.edu]

  Mutations in the insulin receptor ( I NSR ) gene may result in a broad range of phenotypes such as severe autosomal recessive Donohue syndrome (Leprechaunism), which combines somatic anomalies and dysmorphic features with hyperinsulinaemia, hypertrichosis [journals.viamedica.pl]

• Urticaria

  While treating psoriasis patients, screening for metabolic syndrome and cardiovascular risk factors is advised. [14] Insulin reactions may be local (erythema or urticarial pruritic nodules) or systemic (generalized urticaria, rarely anaphylaxis). [e-ijd.org]

• Dysmenorrhea

  Metabolic impairments, primarily in the form of diabetes mellitus, but also hirsutism and dysmenorrhea in women, typically starts during early years of life. [symptoma.com]

  […] skin Skin infection [ more ] 0100658 Congestive heart failure Cardiac failure Cardiac failures Heart failure [ more ] 0001635 Coronary artery atherosclerosis Plaque build-up in arteries supplying blood to heart 0001677 Cranial nerve paralysis 0006824 Dysmenorrhea [rarediseases.info.nih.gov]

• Labial Hypertrophy

  In type 2 familial lipodystrophy, the trunk is also affected with the exception of the vulva, giving an appearance of labial hypertrophy. [ncbi.nlm.nih.gov]

The diagnostic workup must comprise a thorough patient history that might reveal a familial presence of symptoms and a thorough physical examination that will identify the distribution of adipose tissue. Laboratory workup reveals hypertriglyceridemia and insulin resistance [3], but because clinical features of this rare genetic syndrome strongly point to an endocrine disease, the diagnosis can be easily missed [2]. For this reason, the role of history taking in these patients is of vital importance.

• Hypertriglyceridemia

  Lipatrophic diabetes, also referred to as familial partial lipodystrophy, is a rare disease that is metabolically characterized by hypertriglyceridemia and insulin resistance. [ncbi.nlm.nih.gov]

  Complications include hypertension, insulin resistance and hypertriglyceridemia. The gene causing this condition is not yet known. This form was first described in 1975. [en.wikipedia.org]

  In fact, the hypertriglyceridemia was so severe that 64% of FPLD1 subjects with hypertriglyceridemia had a history of pancreatitis due to chylomicronemia syndrome ( 23 ). [doi.org]

• Dyslipidemia

  FPLD 2 should be considered in the differential diagnosis of diabetes, dyslipidemia, steatohepatitis, acanthosis nigricans and polycystic ovary syndrome. [ncbi.nlm.nih.gov]

  A major addition to the literature, Dyslipidemias: Pathophysiology, Evaluation and Management is a gold-standard level reference for all clinicians who are challenged to provide the best care and new opportunities for patients with dyslipidemias. [books.google.com]

• Hyperinsulinemia

  FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes, dyslipidemia, and hypertension. [ncbi.nlm.nih.gov]

  The Investigators will also study the rate of de-novo protein synthesis to determine if hyperinsulinemia affects both muscle protein anabolism and catabolism. [clinicaltrials.gov]

  […] clinical examination, analysis of fat distribution by imaging (MRI, CT-scan and whole-body dual-energy X-ray absorptiometry) and evaluation of metabolic status (hypertriglyceridemia, low levels of high density lipoprotein (HDL)-cholesterol in the blood, hyperinsulinemia [orpha.net]

• Hyperglycemia

  Findings include full and rounded face, xanthomata, acanthosis nigricans, and insulin-resistant hyperglycemia. [medical-dictionary.thefreedictionary.com]

  CONCLUSION: Metreleptin replacement therapy is equally effective in FPLD patients with both SH and MH in reducing serum and hepatic triglyceride levels, but did not improve hyperglycemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT00457938 . [ncbi.nlm.nih.gov]

  Risk factors for hypoglycemia in diabetes Magnitude of the clinical problem of hypoglycemia in diabetes Prevention and treatment of hypoglycemia in diabetes Perspective on hypoglycemia in diabetes Acknowledgments 34 Diabetic ketoacidosis Hyperosmolar hyperglycemia [books.google.com]

  Conclusion: Well-controlled diabetes decreases the prevalence of DM-specific cutaneous disorders associated with chronic hyperglycemia. [e-ijd.org]

  Finally, fasting hyperglycemia—frank diabetes—occurs many years later and most likely reflects pancreatic β-cell failure in the context of chronic insulin resistance. [circ.ahajournals.org]

Management of diabetes mellitus and hyperlipidemia is the mainstay of therapy, whereas leptin replacement therapy is currently under review for use in treating patients with various forms of lipodystrophies [3].

In rare cases, marked hypertriglyceridemia can induce acute pancreatitis and hepatic steatosis, whereas myopathy and cardiomyopathy have been documented as well [3] [5].

Mutations in genes that code for intermediate filaments proteins that serve as constituents of nuclear membranes, known as lamins, are the underlying cause of FPLD [1]. Lamin A and C mutations are transferred by an autosomal dominant pattern of inheritance and the condition is exclusively found in more than one family member [3]. Most recent studies have discovered that mutations in one of the nuclear receptors, the peroxisome proliferator-activated receptor gamma (PPARG), are also associated with the onset of FPLD [4].

FPLD is a very rare condition and only isolated case reports or case series are the sources of data regarding this condition [1] [2] [3] [4] [5]. Neither gender nor ethnic predilection has been established, whereas risk factors are yet to be determined.

Lamins are recognized as essential nuclear membrane proteins and they are coded by Lamin A and C genes [2]. In the setting of mutations, their structure is disrupted and through still unknown mechanisms, individuals suffer from adipose tissue loss and develop a clinical presentation of metabolic syndrome [2] [3].

At this point, prevention strategies against FPLD do not exist.

Familial partial lipodystrophy (FPLD, also known as Köbberling–Dunnigan syndrome), is a rare autosomal dominant genetic disorder that belongs to the group of laminopathies, disorders that are associated with mutations in the lamin A/C gene (LMNA and LMNC, respectively) [1]. The pathogenesis model remains unclear but is thought that mutations in these intermediate filament proteins lead to fat loss and development of insulin resistance [2]. There are two main clinical types: type I, in which fat loss predominantly occurs on the extremities, with normal or slightly increased distribution of adipose tissue in the thorax and the head and neck area; and type II, characterized by loss of fat from both the limbs and the trunk and its accumulation in the neck region [2]. To make the diagnosis, it is necessary to obtain a thorough patient history, perform a detailed physical examination and evaluate serum lipid and glucose levels, as diabetes mellitus and dyslipidemia are frequent findings in these patients [3]. Treatment focuses on managing symptoms, mainly through lipid-lowering drugs and insulin [3].

Familial partial lipodystrophy (FPLD) is a rare genetic disease characterized by loss of fat tissue due to mutations of proteins that serve as building blocks of cell membranes. FPL is transferred by an autosomal dominant pattern of inheritance, meaning that parents will almost certainly transfer the mutated gene to their children and the majority of reported cases involve more than one family member. The disease most frequently presents with loss of fat in the extremities and a normal or somewhat increased amount of fat in the chest and the head and neck area and metabolic diseases such as diabetes mellitus are commonly encountered. Symptoms start in early childhood and the diagnosis can be made by obtaining a detailed patient history that reveals the presence of symptoms in other family members, while blood tests show elevations of triglycerides and glucose. Treatment is currently aimed at controlling diabetes and high lipid levels.

1. Drac H, Madej-Pilarczyk A, Gospodarczyk-Szot K, Gaweł M, Kwieciński H, Hausmanowa-Petrusewicz I. Familial partial lipodystrophy associated with the heterozygous LMNA mutation 1445G>A (Arg482Gln) in a Polish family. Neurol Neurochir Pol. 2010;44(3):291-296.
2. Herbst KL, Tannock LR, Deeb SS, Purnell JQ, Brunzell JD, Chait A. Köbberling type of familial partial lipodystrophy: an underrecognized syndrome. Diabetes Care. 2003 Jun;26(6):1819-1824.
3. Handelsman Y, Oral EA, Bloomgarden ZT, et al. The clinical approach to the detection of lipodystrophyy - An AACE concensus statement. Endocr Pract 2013;19(1):107-116.
4. Demir T, Onay H, Savage DB, Temeloglu E, Uzum AK, Kadioglu P, et al. Familial partial lipodystrophy linked to a novel peroxisome proliferator activator receptor -γ (PPARG) mutation, H449L: a comparison of people with this mutation and those with classic codon 482 Lamin A/C (LMNA) mutations. Diabet Med. 2016;33(10):1445-1450.
5. Jackson SNJ, Howlett TA, McNally PG, O’Rahilly S, Trembath RC. Dunnigan-Kobberling syndrome: an autosomal dominant form of partial lipodystrophy. QJM. 1997;90(1):27-36.