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
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 ...
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
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 ...
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
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 ...
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
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 ...
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.
See also
*
Lipodystrophy
Lipodystrophy syndromes are a group of genetic or acquired disorders in which the body is unable to produce and maintain healthy fat tissue. The medical condition is characterized by abnormal or degenerative conditions of the body's adipose tissue. ...
*
List of cutaneous conditions
Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against t ...
References
External links
{{Transcription factor/coregulator deficiencies
Conditions of the subcutaneous fat
Syndromes