Marfanoid–progeroid–lipodystrophy syndrome (MPL), also known as Marfan lipodystrophy syndrome (MFLS) or progeroid fibrillinopathy, is an extremely rare
medical condition which manifests as a variety of
symptoms including those usually associated with
Marfan syndrome, an appearance resembling that seen in
neonatal progeroid syndrome (NPS; also known as Wiedemann–Rautenstrauch syndrome), and severe
partial lipodystrophy.
It is a
genetic condition that is caused by
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, ...
s in the ''
FBN1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
, which encodes
profibrillin, and affects the
cleavage products of profibrillin,
fibrillin-1, a
fibrous structural protein, and
asprosin, a
glucogenic protein hormone.
As of 2016, fewer than 10 cases of the condition have been reported.
and
Abby Solomon have become known publicly through the media for having the condition.
In addition to severe
lipodystrophy (loss of
adipose tissue), individuals with MPL show a concomitant marked loss of
lean tissue mass, which also contributes to their "skinny" appearance.
Based on visual inspection, it was originally thought that the lipodystrophy associated with MPL was
generalized.
However, it appears in fact to be partial, being confined to the
face,
distal extremities, and the
paravertebral and
lateral
Lateral is a geometric term of location which may also refer to:
Biology and healthcare
* Lateral (anatomy), a term of location meaning "towards the side"
* Lateral cricoarytenoid muscle, an intrinsic muscle of the larynx
* Lateral release ( ...
regions of the
buttocks.
Normal amounts of
subcutaneous fat are found in the
torso
The torso or trunk is an anatomical terminology, anatomical term for the central part, or the core (anatomy), core, of the body (biology), body of many animals (including human beings), from which the head, neck, limb (anatomy), limbs, tail an ...
over the
chest and
abdomen
The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...
.
As such, the
breast
The breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...
s are normal in females with MPL.
Individuals with MPL have an appearance of being prematurely
aged, but this is not due to actual early aging and is instead due to their paucity of
subcutaneous fat.
As such, MPL is not truly a form of
progeria.
In 2016, it was discovered that the partial lipodystrophy associated with MPL is caused by loss of the
C-terminal domain cleavage product of profibrillin and novel glucogenic protein hormone, which has been named asprosin.
Due to asprosin deficiency, individuals with MPL eat less, and do not
gain weight or develop symptoms of
diabetes like
insulin resistance.
MPL patients burn less energy than normal individuals, but also consume less, and their net
energy balance is moderately reduced.
[Duerrschmid C, He Y, Wang C, Li C, Bournat J, Romere C, Saha PK, Lee M, Phillips KJ, Jain M, Jia P, Zhao Z, Farias M, Wu Q, Milewicz DM, Sutton VR, Moore DM, Butte NF, Krashes MJ, Xu Y, and Chopra AR (2017) - "Asprosin Activates the Hypothalamic Hunger-Circuitry" - article under consideration for publication as of 8/30/2017.] In contrast to MPL patients, whose asprosin is undetectable in the blood, individuals with
obesity
Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
and diabetes have elevated levels of asprosin.
As such, ''FBN1'' has been nicknamed the "thin gene", and
drug development for targeted inhibition of asprosin signaling is considered to be an "unusually promising" potential therapeutic route in the treatment of obesity and diabetes.
References
External links
{{DEFAULTSORT:Marfanoid-progeroid-lipodystrophy syndrome
Conditions of the subcutaneous fat
Rare genetic syndromes
Rare syndromes