Familial partial lipodystrophy, also known as Köbberling–Dunnigan syndrome, is a rare genetic metabolic condition characterized by the loss of

subcutaneous fat The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and mac ...

. FPL also refers to a rare metabolic condition in which there is a loss of subcutaneous fat in the arms, legs and lower torso. The upper section of the body, face, neck, shoulders, back and trunk carry an excess amount of fat. As the body is unable to store fat correctly this leads to fat around all the vital organs and in the blood (triglycerides). This results in heart problems, cirrhosis of the liver, lipoatrophic diabetes, and pancreatitis, along with various other complications.

Types

Presentation

Type 1 is believed to be underdiagnosed.

Genetics

A mutations in a number of genes have been associated with this condition.

Mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

s associated with FPL have been reported in ''

LMNA Pre-lamin A/C or lamin A/C is a protein that in humans is encoded by the ''LMNA'' gene. Lamin A/C belongs to the lamin family of proteins. Function In the setting of ZMPSTE24 deficiency, the final step of lamin processing does not occur, res ...

'' (lamin A/C), ''

PPARG Peroxisome proliferator- activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a tran ...

'' (PPARγ), ''

AKT2 AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the ''AKT2'' gene. It influences metabolite storage as part of the insulin signal transduction pathway. Function This gene is a putative o ...

'' (AKT serine/threonine kinase 2), ''

PLIN1 Perilipin, also known as lipid droplet-associated protein, Perilipin 1, or PLIN, is a protein that, in humans, is encoded by the ''PLIN'' gene. The perilipins are a family of proteins that associate with the surface of lipid droplets. Phosphoryla ...

'' (perilipin-1), and '' CIDEC'' (cell-death-inducing DFFA-like effector B). Six types (1-6) have been described. Types 1-5 are inherited in an autosomal dominant fashion. Type 1 (Kobberling variety, FPL1) is very rare and has only been reported in women to date. Fat loss is confined to the limbs and mostly in the distal parts. Central obesity may be present. Complications include hypertension, insulin resistance and hypertriglyceridemia. The gene causing this condition is not yet known. This form was first described in 1975. Type 2 (Dunnigan Variety, FPL2) is the most common form and is due to mutations in the

gene. Over 500 cases have been reported to date. Development up to puberty is normal. Fat is then gradually lost in is the limbs and trunk. Fat may accumulate around the face and between the shoulder blades. Insulin resistance is common. Other conditions associated with this condition include

acanthosis nigricans Acanthosis nigricans is a medical sign characterised by brown-to-black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds, such as the posterior and lateral folds of the neck, the armpits, groin, navel, fore ...

, fatty liver, hypertriglyceridemia and

polycystic ovary syndrome Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and no ...

in women. There is an increased risk of coronary heart disease.

Cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...

and muscular dystrophy may occur rarely.

Xanthoma A xanthoma (pl. xanthomas or xanthomata) (condition: xanthomatosis) is a deposition of yellowish cholesterol-rich material that can appear anywhere in the body in various disease states. They are cutaneous manifestations of lipidosis in which lip ...

and nail changes may occur. Type 3 is due to mutations in the

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

gene. It is rare with only a small number of cases reported. Fat loss tends to affect the lower limbs and buttocks. Insulin resistance and hypertriglyceridemia occur. Calf muscular hypertrophy may occur. Type 5 is due to mutations in the

gene. It has been reported in four patients all members of the same family. Fat loss affects the upper and lower limbs. The patients also had hypertension, insulin resistance and hypertriglyceridemia. Type 6 due to mutations in the CIDEC gene. It is inherited in an autosomal recessive fashion and has been reported in only one patient to date. Features included fat loss, severe insulin resistance, fatty liver, acanthosis nigricans and diabetes. Another gene that has been associated with this condition is

AGPAT2 1-acyl-sn-glycerol-3-phosphate acyltransferase beta is an enzyme that in humans is encoded by the ''AGPAT2'' gene. Function This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. The protein is located within th ...

.Broekema MF, Massink MPG, De Ligt J, Stigter ECA, Monajemi H, De Ridder J, Burgering BMT, van Haaften GW, Kalkhoven E (2018) A single complex Agpat2 allele in a patient With partial lipodystrophy. Front Physiol 9:1363. doi: 10.3389/fphys.2018.01363.

Diagnosis

Treatment

Prevalence

This not known with certainty but is estimated to be about one per million. It appears to be more common in females than males.

References

External links

{{Transcription factor/coregulator deficiencies Conditions of the subcutaneous fat Syndromes