What are the 4 main types of lipodystrophies?
Congenital generalized lipodystrophy (Berardinelli-Selp syndrome), Familial partial lipodystrophy (Köbberling-Dunnigan syndrome), Acquired generalized lipodystrophy (Lawrence syndrome), Acquired partial lipodystrophy (Barraquer-Simons syndrome).
What are the two acquired lipodystrophies?
Acquired generalized lipodystrophy (Lawrence syndrome), Acquired partial lipodystrophy (Barraquer-Simons syndrome).
What are the genes involved in Congenital generalized lipodystrophy and what type of inheritance do they display?
AR
- AGPAT2 (type I)
- BSCL2/seipin (type II)
- CAV1 (type III)
Where is congenital generalized lipodystrophy most commonly seen?
Brazil
Clinical features of congenital generalized lipodystrophy?
Loss of fat in the face (pre-auricular especially, trunk, extremities, viscera and can affect palmoplantar/retroorbital/tongue/breasts/vulva/peri-articular areas as well
-Also can see acanthosis nigricans, hypertrichosis, xanthomas
- Muscular hypertrophy appearance
Osteosclerotic and lytic skeletal changes
- Masculinization in women/enlarged genitalia in kids only
sx’s start at birth
Which of the congenital generalized lipodystrophies have bone marrow involvement?
Types 1/2 lack bone marrow fat, whereas type 3/4 have normal bone marrow fat
What lab abnormalities/systemic findings can be seen in congenital generalized lipodystrophy?
Diabetes/insulin resistance common (metabolic syndrome)
- Increased triglycerides, decreased HDL
- Vitamin D resistance in type 3
- PCOS, infertility (woman)
- Hypertrophic cardiomyopathy (a main cause of death, lifespan ~32 yrs)[Increased in type 2]
- Can also see atherosclerosis, liver failure/fatty liver/cirrhosis, acute pancreatitis, proteinuric nephropathy, mental retardation (increased in type 2)
What are the genes involved in the familial partial lipodystrophy and what is the mode of inheritance?
AD
Genes: LMNA, PPARgamma (milder clinical features but worse metabolic features), AKT2, PLIN1
What are the clinical features of familial partial lipodystrophy?
Loss of fat on extremities/buttocks and can have trunk involvement (anterior more than posterior)
- Increased fat on the face/neck, and labia majora
- Muscular hypertrophy appearance w/ prominent veins
- Also see tuberous xanthomas, acanthosis nigricans, hirsutism
When do the features of familial partial lipodystrophy start as compared to congenital generalized lipodystrophy?
First signs of dz start around puberty as compared to birth for congenital generalized lipodystrophy
What are the lab abnormalities/systemic findings of familial partial lipodystrophy?
Diabetes/insulin resistance more common as compared to congenital generalized
- Increased triglycerides, decreased HDL (worse w/ PPARgamma)
- Acute pancreatitis, fatty liver/cirrhosis, menstrual issues, PCOS, atherosclerosis and hypertrophic cardiomyopathy
- worse in women
- Subtype w/ mandibulofacial dysplasia (LMNA or ZMPSTE24 mutation
What are the clinical features of acquired generalized lipodystrophy?
Loss of at on face, trunk, extremities (Including palms/soles)
- Loss of visceral fat but bone marrow fat preserved, unlike the types 1/2 congenital generalized lipodystrophy
- Can also have acanthosis nigricans, hyperpigmentation, eruptive xanthomas, hirsutism
muscular appearance due to loss of fat
What are the systemic findings of acquired generalized lipodystrophy?
diabetes/insulin resistance more common
- Increased tryglycerides and decreased HDL
- 30% have autoimmune connective tissue dz and 1/4 may have a preceding panniculitis
- clitoromegaly, PCOS, menstrual issues
- Coronary artery dz/PVD, organomegaly, fatty liver cirrhosis (can be worse and more fatal than the generalized congenital
- Does have the hypertrophic cardiomyopathy
When does acquired generalized lipodystrophy start?
Usually starts in childhood/adolescence (7 y/o in panniculitis variant, 15 y/o in autoimmune variant, 20 y/o in idiopathic variant)
What are the suspected etiologies of acquired partial lipodystrophy?
Sporadic vs AD/LMNB2
- It is linked to infections and autoimmune dz
What are the clinical features of acquired partial lipodystrophy?
F>>M
- Loss of fat on face (cadaveric facies is a buzz-word here), upper extremities, trunk, (spreads in a cephalocaudal direction, sparing lower extremities)
- Increased fat in hips, legs, gluteal region
- Like the other can see acanthosis nigricans, hirsutism
What are some systemic findings in acquired partial lipodystrophy?
Increased triglycerides and DM2/insulins resistance but is less common than in the other lipodystrophies
- May be associated w/ infection and autoimmune connective tissue disease, but less so than acquired generalized
- Membranoproliferative glomerulonephritis is a major association: occurs several years after lipodystrophy in 20% of pts.
- Decreased C3 and increased C3 nephritic factor which is a polyclonal IgG and binds C3 –> activates alternative complement pathway leading to adipocyte death and increased N. Meningitides infections
What are the clinical findings of lipodystrophy seen w/ HIV/ART therapy?
Decreased fat on the extremities/face and increased fat in torso, almost a cushingoid appearances)
What is the timeline for lipodystrophy seen w/ HIV/ART therapy?
Seen 2 months - 2 years after starting therapy
