Acquired partial lipodystrophy, also called Barraquer-Simons syndrome, is a rare acquired partial lipodystrophy with progressive cephalocaudal loss of subcutaneous adipose tissue from the face, neck, upper limbs, and trunk while lower-extremity adipose tissue is relatively spared. Human cohort and tissue evidence supports an immune-mediated complement phenotype, with low serum C3, C3 nephritic factor and other complement autoantibodies, elevated factor D/adipsin in some patients, and local complement-directed adipose-tissue injury. Important complications include autoimmune disease association, complement-mediated renal disease such as membranoproliferative glomerulonephritis/C3 glomerulopathy, variable metabolic complications, and quality-of-life impact from lipoatrophy.
Ask a research question about Acquired Partial Lipodystrophy. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Acquired Partial Lipodystrophy
category: Complex
creation_date: "2026-05-11T00:00:00Z"
updated_date: "2026-05-20T18:11:42Z"
description: >-
Acquired partial lipodystrophy, also called Barraquer-Simons syndrome, is a
rare acquired partial lipodystrophy with progressive cephalocaudal loss of
subcutaneous adipose tissue from the face, neck, upper limbs, and trunk while
lower-extremity adipose tissue is relatively spared. Human cohort and tissue
evidence supports an immune-mediated complement phenotype, with low serum C3,
C3 nephritic factor and other complement autoantibodies, elevated factor
D/adipsin in some patients, and local complement-directed adipose-tissue
injury. Important complications include autoimmune disease association,
complement-mediated renal disease such as membranoproliferative
glomerulonephritis/C3 glomerulopathy, variable metabolic complications, and
quality-of-life impact from lipoatrophy.
disease_term:
preferred_term: acquired partial lipodystrophy
term:
id: MONDO:0012104
label: acquired partial lipodystrophy
parents:
- acquired lipodystrophy
- partial lipodystrophy
synonyms:
- APLD
- Barraquer-Simons syndrome
- partial acquired lipodystrophy
- progressive cephalothoracic lipodystrophy
definitions:
- name: Clinical fat-loss pattern
definition_type: CASE_DEFINITION
description: >-
Acquired partial lipodystrophy is recognized by gradual loss of upper-body
subcutaneous adipose tissue, especially face, neck, upper limbs, thorax, and
trunk, with sparing of the lower extremities.
scope: Clinical recognition of classic Barraquer-Simons syndrome
evidence:
- reference: PMID:32890433
reference_title: "Evidence of ongoing complement activation on adipose tissue from an 11-year-old girl with Barraquer-Simons syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Barraquer-Simons syndrome (BSS), a form of acquired partial lipodystrophy,
is a rare condition characterized by gradual loss of adipose tissue from
the upper body, keeping intact the white adipose tissue of the lower
extremities.
explanation: >-
This human tissue case report gives a compact clinical definition of the
acquired partial lipodystrophy fat-loss pattern.
- reference: PMID:32404319
reference_title: Lipotransfer provides effective soft tissue replacement for acquired partial lipodystrophy.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
It is a rare disease characterised by a gradual and progressive onset of
lipoatrophy limited to the face, neck, upper limbs, thorax and abdomen
and sparing the lower extremities.
explanation: >-
This case report independently supports the characteristic regional
distribution and progression of lipoatrophy.
epidemiology:
- name: Rare acquired lipodystrophy in referral cohorts
description: >-
Acquired partial lipodystrophy is one of the rare acquired lipodystrophy
syndromes encountered in specialist lipodystrophy and insulin-resistance
pathways. Published pathway data show long diagnostic delays across these
rare syndromes.
evidence:
- reference: PMID:38678257
reference_title: "Diagnostic and referral pathways in patients with rare lipodystrophy and insulin-resistance syndromes: key milestones assessed from a national reference center."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A cohort of 292 patients was analyzed, including 208 women, with the
following diagnosis: Familial Partial LipoDystrophy (FPLD, n = 124,
including n = 67 FPLD2/Dunnigan Syndrome); Acquired lipodystrophy
syndromes (n = 98, with n = 13 Acquired Generalized Lipodystrophy, AGL);
explanation: >-
The national reference-center cohort documents acquired lipodystrophy
syndromes among rare lipodystrophy and insulin-resistance referrals.
progression:
- phase: Childhood or adult onset with progressive cephalocaudal spread
age_range: Childhood to adulthood
notes: >-
The fat-loss pattern may begin in childhood and progress gradually from the
face and neck to upper extremities and trunk. Delayed recognition is common
in rare lipodystrophy pathways.
evidence:
- reference: PMID:27402657
reference_title: "Barraquer-Simons syndrome: a unique patient's perspective on diagnosis, disease progression and recontouring treatment."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This case report describes a female patient diagnosed with
Barraquer-Simons syndrome, a rare form of acquired partial lipodystrophy
characterised by symmetrical loss of adipose tissue from face, neck,
upper extremities and the trunk with onset in early childhood.
explanation: >-
The patient-perspective case report documents early-childhood onset and
the symmetrical upper-body distribution.
- reference: PMID:38678257
reference_title: "Diagnostic and referral pathways in patients with rare lipodystrophy and insulin-resistance syndromes: key milestones assessed from a national reference center."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Improving knowledge to reduce diagnostic delay is an important objective
of the PRISIS reference center.
explanation: >-
Rare lipodystrophy pathway data support delayed diagnosis after first
symptoms, relevant to APL recognition and specialist referral.
pathophysiology:
- name: Alternative Complement Pathway Dysregulation
description: >-
Acquired partial lipodystrophy is strongly associated with alternative
complement pathway dysregulation. C3 nephritic factor and other
complement-directed autoantibodies can stabilize complement activation,
leading to C3 consumption, low serum C3, and persistent complement
activation.
biological_processes:
- preferred_term: complement activation, alternative pathway
modifier: INCREASED
term:
id: GO:0006957
label: complement activation, alternative pathway
- preferred_term: complement activation
modifier: DYSREGULATED
term:
id: GO:0006956
label: complement activation
evidence:
- reference: PMID:31924231
reference_title: Immunological features of patients affected by Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
BACKGROUND: C3 hypocomplementemia and the presence of C3 nephritic factor
(C3NeF), an autoantibody causing complement system over-activation, are
common features among most patients affected by Barraquer-Simons syndrome
(BSS), an acquired form of partial lipodystrophy.
explanation: >-
The 13-patient immunology cohort identifies low C3 and C3NeF-mediated
complement over-activation as common features of BSS/APL.
- reference: PMID:31924231
reference_title: Immunological features of patients affected by Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Moreover, the finding of autoantibodies targeting complement system
proteins points to complement dysregulation as a central pathological
event in the development of BSS.
explanation: >-
The cohort authors explicitly interpret complement autoantibodies as a
central pathological event.
downstream:
- target: Adipose Complement-Directed Injury
description: >-
Persistent complement dysregulation can produce local complement
activation and complement-directed injury in affected adipose tissue.
evidence:
- reference: PMID:32890433
reference_title: "Evidence of ongoing complement activation on adipose tissue from an 11-year-old girl with Barraquer-Simons syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Simultaneous detection of IgG, C3, C5a and C5b-9 proved the ongoing
complement activity and complement-directed injury within the adipose
tissue.
explanation: >-
Local IgG, C3, C5a, and C5b-9 detection supports the edge from
complement dysregulation to adipose complement-directed injury.
- target: Complement-Mediated Glomerular Disease Risk
description: >-
Alternative pathway dysregulation also links APL/BSS to C3
glomerulopathy and membranoproliferative glomerulonephritis.
evidence:
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The mechanistic connection with complement activation is further
reinforced by the fact that 20% of BSS patients eventually develop C3G
[1].
explanation: >-
The BSS full-text evidence supports the edge from complement activation
to later C3 glomerulopathy risk.
- target: Decreased circulating complement C3 concentration
causal_link_type: DIRECT
description: >-
Ongoing alternative-pathway activation consumes complement C3, producing
the low circulating C3 phenotype used in BSS/APL workup.
evidence:
- reference: PMID:31924231
reference_title: Immunological features of patients affected by Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
C3, C4 and FB levels were significantly reduced in patients with BSS as
compared with healthy subjects.
explanation: >-
The immunology cohort supports reduced circulating C3 as a downstream
feature of complement dysregulation in BSS/APL.
- target: Low serum complement C3
causal_link_type: DIRECT
description: >-
Low serum complement C3 is the biochemical readout of alternative
complement pathway consumption in BSS/APL.
evidence:
- reference: PMID:31924231
reference_title: Immunological features of patients affected by Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CONCLUSIONS: Our results confirmed the association between BSS,
autoimmunity and C3 hypocomplementemia.
explanation: >-
The cohort conclusion supports low serum C3 as a biochemical correlate
of BSS/APL complement dysregulation.
- target: Autoimmunity
causal_link_type: UNKNOWN
description: >-
BSS/APL cohorts show autoimmune disease and complement autoantibody
enrichment alongside complement dysregulation.
evidence:
- reference: PMID:31924231
reference_title: Immunological features of patients affected by Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinical data showed high prevalence of autoimmune diseases (38.5%), the
majority of patients (61.5%) being positive for at least one of the
autoantibodies tested.
explanation: >-
Human cohort data support autoimmunity as an associated branch of the
complement-dysregulated BSS/APL phenotype.
- name: Factor D/Adipsin Amplification in Adipose Tissue
description: >-
Complement factor D, also called adipsin, is a key alternative-pathway
protease largely produced by adipocytes and macrophages in adipose tissue.
Elevated factor D in BSS may amplify local complement activation in the
adipose-tissue environment and has been proposed as a diagnostic biomarker.
biological_processes:
- preferred_term: complement activation, alternative pathway
modifier: INCREASED
term:
id: GO:0006957
label: complement activation, alternative pathway
cell_types:
- preferred_term: adipocyte
term:
id: CL:0000136
label: adipocyte
- preferred_term: macrophage
term:
id: CL:0000235
label: macrophage
locations:
- preferred_term: subcutaneous adipose tissue
term:
id: UBERON:0002190
label: subcutaneous adipose tissue
evidence:
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Complement Factor D (FD) is a serine protease with a crucial role in the
activation of the alternative pathway of the complement system, which is
mainly synthesized by adipose tissue.
explanation: >-
The factor D cohort paper links FD/adipsin to alternative pathway
activation and adipose-tissue production.
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We found significantly elevated FD levels in BSS cases compared with the
remaining cohorts (p < 0.001).
explanation: >-
The case-control cohort supports elevated circulating factor D in BSS.
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Our results suggest that FD could be a reliable diagnostic biomarker
involved in the pathophysiology of BSS by promoting unrestrained local
complement system activation in the adipose tissue environment.
explanation: >-
The authors explicitly propose FD as both a biomarker and a contributor
to local adipose complement activation.
downstream:
- target: Adipose Complement-Directed Injury
description: >-
Elevated FD/adipsin can accelerate local alternative pathway activation
in adipose tissue already exposed to C3NeF-associated dysregulation.
evidence:
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Our results suggest that FD could be a reliable diagnostic biomarker
involved in the pathophysiology of BSS by promoting unrestrained local
complement system activation in the adipose tissue environment.
explanation: >-
This supports the edge from elevated FD/adipsin to local adipose
complement activation and injury.
- target: Complement factor D/adipsin
causal_link_type: DIRECT
description: >-
Elevated factor D/adipsin is a measurable marker of this adipose-linked
alternative-complement amplification branch.
evidence:
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We found significantly elevated FD levels in BSS cases compared with the
remaining cohorts (p < 0.001).
explanation: >-
The case-control cohort directly supports elevated FD/adipsin as a
biochemical readout of the BSS/APL complement-amplification branch.
- name: Adipose Complement-Directed Injury
description: >-
Active affected adipose tissue shows atrophied and dead adipocytes,
abnormal extracellular matrix production, macrophage infiltration, and
local IgG/C3/C5a/C5b-9 deposition, supporting direct complement-mediated
tissue injury as a mechanism for progressive lipoatrophy.
biological_processes:
- preferred_term: complement activation
modifier: INCREASED
term:
id: GO:0006956
label: complement activation
- preferred_term: inflammatory response
modifier: INCREASED
term:
id: GO:0006954
label: inflammatory response
- preferred_term: extracellular matrix organization
modifier: INCREASED
term:
id: GO:0030198
label: extracellular matrix organization
- preferred_term: apoptotic process
modifier: INCREASED
term:
id: GO:0006915
label: apoptotic process
cell_types:
- preferred_term: adipocyte
modifier: DECREASED
term:
id: CL:0000136
label: adipocyte
- preferred_term: macrophage
modifier: INCREASED
term:
id: CL:0000235
label: macrophage
locations:
- preferred_term: subcutaneous adipose tissue
modifier: DECREASED
term:
id: UBERON:0002190
label: subcutaneous adipose tissue
evidence:
- reference: PMID:32890433
reference_title: "Evidence of ongoing complement activation on adipose tissue from an 11-year-old girl with Barraquer-Simons syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Adipose tissue from the patient showed atrophied and dead adipocytes, an
abnormal production of extracellular matrix, and a remarkable accumulation
of infiltrating CD68 macrophages and adipocyte precursors (marked by
c-Kit positiveness).
explanation: >-
Human affected adipose tissue demonstrates adipocyte loss, extracellular
matrix remodeling, and macrophage-rich inflammation.
- reference: PMID:32890433
reference_title: "Evidence of ongoing complement activation on adipose tissue from an 11-year-old girl with Barraquer-Simons syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Simultaneous detection of IgG, C3, C5a and C5b-9 proved the ongoing
complement activity and complement-directed injury within the adipose
tissue.
explanation: >-
Local immunostaining provides direct evidence for complement activity and
complement-directed injury in adipose tissue.
- reference: PMID:32890433
reference_title: "Evidence of ongoing complement activation on adipose tissue from an 11-year-old girl with Barraquer-Simons syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Our results showed the first evidence that the complement system
hyperactivation occurs within the adipose tissue and is linked with fat
loss in patients with BSS.
explanation: >-
The study directly links adipose complement hyperactivation with fat loss
in BSS.
downstream:
- target: Progressive Upper-Body Lipoatrophy
causal_link_type: DIRECT
description: >-
Complement-directed injury to adipocytes in affected subcutaneous adipose
depots produces the clinical upper-body lipoatrophy phenotype.
evidence:
- reference: PMID:32890433
reference_title: "Evidence of ongoing complement activation on adipose tissue from an 11-year-old girl with Barraquer-Simons syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Our results showed the first evidence that the complement system
hyperactivation occurs within the adipose tissue and is linked with fat
loss in patients with BSS.
explanation: >-
The affected adipose-tissue study directly supports complement
hyperactivation as linked with fat loss.
- target: Loss of facial adipose tissue
causal_link_type: DIRECT
description: >-
Complement-directed adipocyte injury in affected upper-body depots
manifests clinically as facial adipose-tissue loss.
evidence:
- reference: PMID:27402657
reference_title: "Barraquer-Simons syndrome: a unique patient's perspective on diagnosis, disease progression and recontouring treatment."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This case report describes a female patient diagnosed with
Barraquer-Simons syndrome, a rare form of acquired partial lipodystrophy
characterised by symmetrical loss of adipose tissue from face, neck,
upper extremities and the trunk with onset in early childhood.
explanation: >-
The clinical distribution supports facial fat loss as part of the
downstream upper-body lipoatrophy branch.
- target: Decreased adipose tissue around neck
causal_link_type: DIRECT
description: >-
The cephalocaudal lipoatrophy pattern includes loss of neck
subcutaneous adipose tissue.
evidence:
- reference: PMID:27402657
reference_title: "Barraquer-Simons syndrome: a unique patient's perspective on diagnosis, disease progression and recontouring treatment."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This case report describes a female patient diagnosed with
Barraquer-Simons syndrome, a rare form of acquired partial lipodystrophy
characterised by symmetrical loss of adipose tissue from face, neck,
upper extremities and the trunk with onset in early childhood.
explanation: >-
The case report directly lists neck adipose-tissue loss in the
BSS/APL distribution.
- target: Loss of subcutaneous adipose tissue from upper limbs
causal_link_type: DIRECT
description: >-
Affected upper-body subcutaneous adipose depots include the upper limbs.
evidence:
- reference: PMID:30604443
reference_title: Hyaluronic acid fillers for correcting midface volume deficit in Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The authors report a case of a young woman, who presented with gradual
loss of subcutaneous fat from the face, upper limbs, and trunk.
explanation: >-
The case report supports upper-limb fat loss as part of the downstream
lipoatrophy branch.
- target: Loss of truncal subcutaneous adipose tissue
causal_link_type: DIRECT
description: >-
Affected upper-body subcutaneous adipose depots include the trunk.
evidence:
- reference: PMID:30604443
reference_title: Hyaluronic acid fillers for correcting midface volume deficit in Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The authors report a case of a young woman, who presented with gradual
loss of subcutaneous fat from the face, upper limbs, and trunk.
explanation: >-
The case report supports truncal fat loss as part of the downstream
lipoatrophy branch.
- target: Reduced adipose lipid-storage capacity
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- complement-linked loss of upper-body subcutaneous adipose tissue
description: >-
Loss of subcutaneous adipose tissue reduces safe adipose lipid-storage
capacity and creates the substrate for metabolic complications.
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Lipodystrophies are heterogeneous disorders characterized by varying
degrees of body fat loss and predisposition to insulin resistance and its
metabolic complications.
explanation: >-
Lipodystrophy review evidence supports reduced body fat as the upstream
state predisposing to metabolic complications.
- name: Reduced adipose lipid-storage capacity
description: >-
Loss of subcutaneous adipose tissue reduces adipose lipid-storage capacity.
In lipodystrophy syndromes this predisposes to insulin resistance,
hypertriglyceridemia, and hepatic steatosis, although these complications
are variable in classic acquired partial lipodystrophy.
biological_processes:
- preferred_term: lipid storage
modifier: DECREASED
term:
id: GO:0019915
label: lipid storage
cell_types:
- preferred_term: adipocyte
modifier: DECREASED
term:
id: CL:0000136
label: adipocyte
locations:
- preferred_term: subcutaneous adipose tissue
modifier: DECREASED
term:
id: UBERON:0002190
label: subcutaneous adipose tissue
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Lipodystrophies are heterogeneous disorders characterized by varying
degrees of body fat loss and predisposition to insulin resistance and its
metabolic complications.
explanation: >-
This review links adipose-tissue loss to metabolic complication risk in
lipodystrophy syndromes.
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The metabolic abnormalities associated with lipodystrophy include insulin
resistance, hypertriglyceridemia, and hepatic steatosis.
explanation: >-
The review identifies the downstream metabolic complication triad.
downstream:
- target: Insulin resistance
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- reduced adipose lipid buffering after fat loss
description: >-
Reduced adipose storage capacity predisposes to insulin resistance in
lipodystrophy syndromes.
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Lipodystrophies are heterogeneous disorders characterized by varying
degrees of body fat loss and predisposition to insulin resistance and its
metabolic complications.
explanation: >-
Review evidence supports insulin resistance as a downstream metabolic
complication of body fat loss.
- target: Hypertriglyceridemia
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- reduced adipose lipid buffering after fat loss
description: >-
Reduced adipose storage capacity predisposes to elevated circulating
triglycerides in lipodystrophy syndromes.
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The metabolic abnormalities associated with lipodystrophy include insulin
resistance, hypertriglyceridemia, and hepatic steatosis.
explanation: >-
Review evidence supports hypertriglyceridemia as a metabolic
complication of lipodystrophy.
- target: Hepatic steatosis
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- reduced adipose lipid buffering after fat loss
description: >-
Reduced adipose storage capacity predisposes to ectopic hepatic lipid
accumulation in lipodystrophy syndromes.
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The metabolic abnormalities associated with lipodystrophy include insulin
resistance, hypertriglyceridemia, and hepatic steatosis.
explanation: >-
Review evidence supports hepatic steatosis as a metabolic complication
of lipodystrophy.
- target: Blood triglyceride
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- hypertriglyceridemia secondary to reduced adipose lipid storage
description: >-
Circulating triglyceride concentration reports the
hypertriglyceridemia branch of reduced adipose lipid-storage capacity.
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The metabolic abnormalities associated with lipodystrophy include insulin
resistance, hypertriglyceridemia, and hepatic steatosis.
explanation: >-
Review evidence supports hypertriglyceridemia as the clinical
biochemical consequence reflected by blood triglyceride.
- name: Impaired Adipogenesis and Mitochondrial Gene Expression
description: >-
A human adipose biopsy case report found reduced expression of adipogenesis
and mitochondrial-function genes in affected subcutaneous adipose tissue,
suggesting impaired adipocyte maintenance may accompany complement-driven
tissue loss.
biological_processes:
- preferred_term: fat cell differentiation
modifier: DECREASED
term:
id: GO:0045444
label: fat cell differentiation
cell_types:
- preferred_term: adipocyte
modifier: DECREASED
term:
id: CL:0000136
label: adipocyte
locations:
- preferred_term: subcutaneous adipose tissue
modifier: DECREASED
term:
id: UBERON:0002190
label: subcutaneous adipose tissue
evidence:
- reference: PMID:18752661
reference_title: "Impaired expression of mitochondrial and adipogenic genes in adipose tissue from a patient with acquired partial lipodystrophy (Barraquer-Simons syndrome): a case report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The expression of marker genes of adipogenesis and adipocyte metabolism,
including the master regulator PPARgamma, was down-regulated in
subcutaneous adipose tissue from this patient.
explanation: >-
The case report supports impaired adipogenic gene expression in affected
APL subcutaneous adipose tissue.
- reference: PMID:18752661
reference_title: "Impaired expression of mitochondrial and adipogenic genes in adipose tissue from a patient with acquired partial lipodystrophy (Barraquer-Simons syndrome): a case report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Expression of genes related to mitochondrial function was reduced despite
unaltered levels of mitochondrial DNA.
explanation: >-
The same adipose biopsy supports reduced mitochondrial gene expression in
affected tissue.
downstream:
- target: Progressive Upper-Body Lipoatrophy
description: >-
Impaired adipogenesis and adipocyte metabolic gene expression may weaken
adipocyte maintenance in affected depots.
evidence:
- reference: PMID:18752661
reference_title: "Impaired expression of mitochondrial and adipogenic genes in adipose tissue from a patient with acquired partial lipodystrophy (Barraquer-Simons syndrome): a case report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
It is concluded that adipogenic and mitochondrial gene expression is
impaired in adipose tissue in this patient with acquired partial
lipodystrophy.
explanation: >-
The biopsy case report supports impaired adipogenic and mitochondrial
gene expression in adipose tissue as a contributor to lipoatrophy.
- name: Complement-Mediated Glomerular Disease Risk
description: >-
The same alternative pathway abnormalities implicated in APL/BSS overlap
mechanistically with C3 glomerulopathy and membranoproliferative
glomerulonephritis, where C3NeF stabilizes C3 convertase and can produce
proteinuria, hematuria, hypertension, or kidney failure.
biological_processes:
- preferred_term: complement activation, alternative pathway
modifier: INCREASED
term:
id: GO:0006957
label: complement activation, alternative pathway
locations:
- preferred_term: renal glomerulus
term:
id: UBERON:0000074
label: renal glomerulus
evidence:
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The mechanistic connection with complement activation is further
reinforced by the fact that 20% of BSS patients eventually develop C3G
[1].
explanation: >-
The factor D full-text review context states the reported C3
glomerulopathy risk in BSS.
- reference: PMID:38076230
reference_title: "C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The underlying cause of both DDD and C3Gn is an abnormal activation of
the alternative complement pathway, which can result from acquired or
genetic alteration.
explanation: >-
This C3 glomerulopathy review identifies abnormal alternative pathway
activation as the cause of DDD and C3GN.
- reference: PMID:38076230
reference_title: "C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
In acquired forms of DDD and C3GN, the dysregulation of the alternative
pathway is commonly induced by the presence of C3 nephritic factors
(C3NeFs), which are autoantibodies that stabilize C3 convertase.
explanation: >-
The review links acquired C3 glomerulopathy to the same C3NeF biology
implicated in APL/BSS.
downstream:
- target: Membranoproliferative glomerulonephritis
causal_link_type: DIRECT
description: >-
Alternative-pathway glomerular disease in BSS/APL can present as C3
glomerulopathy within the membranoproliferative glomerulonephritis
spectrum.
evidence:
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The mechanistic connection with complement activation is further
reinforced by the fact that 20% of BSS patients eventually develop C3G
[1].
explanation: >-
APL/BSS evidence supports later C3 glomerulopathy in a subset of
patients.
- reference: PMID:38076230
reference_title: "C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are types of
membranoproliferative glomerulonephritis classified as C3
glomerulopathies.
explanation: >-
The C3 glomerulopathy review maps the renal complication to the
membranoproliferative glomerulonephritis phenotype.
- target: Proteinuria
causal_link_type: DIRECT
description: >-
Complement-mediated glomerular involvement can present with proteinuria.
evidence:
- reference: PMID:38076230
reference_title: "C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The presenting features of these diseases are variable and may include
proteinuria, hematuria, hypertension, or kidney failure.
explanation: >-
The C3 glomerulopathy review supports proteinuria as a downstream renal
manifestation.
phenotypes:
- category: Adipose tissue
name: Progressive Upper-Body Lipoatrophy
frequency: OBLIGATE
diagnostic: true
description: >-
The defining phenotype is progressive lipoatrophy of upper-body
subcutaneous adipose depots with sparing of lower extremities.
phenotype_term:
preferred_term: Lipoatrophy
term:
id: HP:0100578
label: Lipoatrophy
evidence:
- reference: PMID:32404319
reference_title: Lipotransfer provides effective soft tissue replacement for acquired partial lipodystrophy.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
It is a rare disease characterised by a gradual and progressive onset of
lipoatrophy limited to the face, neck, upper limbs, thorax and abdomen
and sparing the lower extremities.
explanation: >-
The case report supports progressive upper-body lipoatrophy as the
defining clinical phenotype.
- category: Adipose tissue
name: Loss of facial adipose tissue
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Facial fat loss is typically part of the cephalocaudal fat-loss pattern and
often drives cosmetic and psychosocial morbidity.
phenotype_term:
preferred_term: Loss of facial adipose tissue
term:
id: HP:0000292
label: Loss of facial adipose tissue
evidence:
- reference: PMID:27402657
reference_title: "Barraquer-Simons syndrome: a unique patient's perspective on diagnosis, disease progression and recontouring treatment."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This case report describes a female patient diagnosed with
Barraquer-Simons syndrome, a rare form of acquired partial lipodystrophy
characterised by symmetrical loss of adipose tissue from face, neck,
upper extremities and the trunk with onset in early childhood.
explanation: >-
The case report directly includes facial adipose-tissue loss in the
characteristic distribution.
- category: Adipose tissue
name: Decreased adipose tissue around neck
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Neck adipose-tissue loss is part of the classic upper-body distribution.
phenotype_term:
preferred_term: Decreased adipose tissue around neck
term:
id: HP:0005995
label: Decreased adipose tissue around neck
evidence:
- reference: PMID:27402657
reference_title: "Barraquer-Simons syndrome: a unique patient's perspective on diagnosis, disease progression and recontouring treatment."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This case report describes a female patient diagnosed with
Barraquer-Simons syndrome, a rare form of acquired partial lipodystrophy
characterised by symmetrical loss of adipose tissue from face, neck,
upper extremities and the trunk with onset in early childhood.
explanation: >-
The case report directly lists neck adipose-tissue loss in the BSS/APL
distribution.
- category: Adipose tissue
name: Loss of subcutaneous adipose tissue from upper limbs
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Upper-limb lipoatrophy follows the face and neck in the cephalocaudal
pattern.
phenotype_term:
preferred_term: Loss of subcutaneous adipose tissue from upper limbs
term:
id: HP:0009056
label: Loss of subcutaneous adipose tissue from upper limbs
evidence:
- reference: PMID:30604443
reference_title: Hyaluronic acid fillers for correcting midface volume deficit in Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The authors report a case of a young woman, who presented with gradual
loss of subcutaneous fat from the face, upper limbs, and trunk.
explanation: >-
The filler case report documents upper-limb subcutaneous fat loss.
- category: Adipose tissue
name: Loss of truncal subcutaneous adipose tissue
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Truncal and thoracoabdominal subcutaneous fat loss are part of the
progressive upper-body phenotype.
phenotype_term:
preferred_term: Loss of truncal subcutaneous adipose tissue
term:
id: HP:0009002
label: Loss of truncal subcutaneous adipose tissue
evidence:
- reference: PMID:30604443
reference_title: Hyaluronic acid fillers for correcting midface volume deficit in Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The authors report a case of a young woman, who presented with gradual
loss of subcutaneous fat from the face, upper limbs, and trunk.
explanation: >-
The filler case report documents truncal subcutaneous fat loss.
- category: Immunologic
name: Decreased circulating complement C3 concentration
frequency: FREQUENT
diagnostic: true
description: >-
Low circulating C3 is a frequent biochemical and immunologic hallmark,
often occurring with C3 nephritic factor.
phenotype_term:
preferred_term: Decreased circulating complement C3 concentration
term:
id: HP:0005421
label: Decreased circulating complement C3 concentration
evidence:
- reference: PMID:31924231
reference_title: Immunological features of patients affected by Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
C3, C4 and FB levels were significantly reduced in patients with BSS as
compared with healthy subjects.
explanation: >-
Human cohort data support reduced circulating C3 and other complement
proteins in BSS.
- category: Immunologic
name: C3 nephritic factor positivity
frequency: FREQUENT
diagnostic: true
description: >-
C3 nephritic factor is the most frequently detected complement
autoantibody in the studied BSS cohort.
phenotype_term:
preferred_term: C3 nephritic factor positivity
term:
id: HP:0030888
label: C3 nephritic factor positivity
evidence:
- reference: PMID:31924231
reference_title: Immunological features of patients affected by Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
C3NeF was the most frequently found autoantibody (69.2% of cases),
followed by anti-C3 (38.5%), and anti-P and anti-FB (30.8% each).
explanation: >-
The immunology cohort provides a percentage for C3NeF positivity in
BSS/APL.
- category: Immune system
name: Autoimmunity
frequency: FREQUENT
description: >-
Autoimmune diseases and complement-directed autoantibodies are common in
studied BSS cohorts.
phenotype_term:
preferred_term: Autoimmunity
term:
id: HP:0002960
label: Autoimmunity
evidence:
- reference: PMID:31924231
reference_title: Immunological features of patients affected by Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinical data showed high prevalence of autoimmune diseases (38.5%), the
majority of patients (61.5%) being positive for at least one of the
autoantibodies tested.
explanation: >-
The cohort supports autoimmune disease association and broader
autoantibody positivity.
- category: Renal
name: Membranoproliferative glomerulonephritis
frequency: OCCASIONAL
description: >-
Complement-mediated glomerular disease is a clinically important
complication of BSS/APL and may present as C3 glomerulopathy or
membranoproliferative glomerulonephritis.
phenotype_term:
preferred_term: Membranoproliferative glomerulonephritis
term:
id: HP:0000793
label: Membranoproliferative glomerulonephritis
evidence:
- reference: PMID:38076230
reference_title: "C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are types of
membranoproliferative glomerulonephritis classified as C3
glomerulopathies.
explanation: >-
The C3 glomerulopathy review maps DDD and C3GN to the
membranoproliferative glomerulonephritis pattern.
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The mechanistic connection with complement activation is further
reinforced by the fact that 20% of BSS patients eventually develop C3G
[1].
explanation: >-
APL/BSS full-text evidence supports C3 glomerulopathy as a later
complication in a subset of patients.
- category: Renal
name: Proteinuria
frequency: OCCASIONAL
description: >-
Proteinuria is a presenting feature of complement-mediated glomerular
disease that should be monitored when BSS/APL patients develop renal
involvement.
phenotype_term:
preferred_term: Proteinuria
term:
id: HP:0000093
label: Proteinuria
evidence:
- reference: PMID:38076230
reference_title: "C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The presenting features of these diseases are variable and may include
proteinuria, hematuria, hypertension, or kidney failure.
explanation: >-
The C3 glomerulopathy review supports proteinuria as a renal surveillance
endpoint in complement-mediated glomerular disease.
- category: Metabolic
name: Insulin resistance
frequency: OCCASIONAL
description: >-
Insulin resistance is part of the variable metabolic complication spectrum
of lipodystrophy, including acquired partial lipodystrophy when adipose
storage capacity is reduced.
phenotype_term:
preferred_term: Insulin resistance
term:
id: HP:0000855
label: Insulin resistance
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Lipodystrophies are heterogeneous disorders characterized by varying
degrees of body fat loss and predisposition to insulin resistance and its
metabolic complications.
explanation: >-
Lipodystrophy review evidence supports insulin resistance as a metabolic
complication of lipodystrophy syndromes.
- category: Metabolic
name: Hypertriglyceridemia
frequency: OCCASIONAL
description: >-
Metabolic complications are variable in acquired partial lipodystrophy but
include hypertriglyceridemia and other insulin-resistance complications
when adipose storage capacity is reduced.
phenotype_term:
preferred_term: Hypertriglyceridemia
term:
id: HP:0002155
label: Hypertriglyceridemia
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The metabolic abnormalities associated with lipodystrophy include insulin
resistance, hypertriglyceridemia, and hepatic steatosis.
explanation: >-
Lipodystrophy review evidence supports hypertriglyceridemia as a
lipodystrophy-associated metabolic complication.
- category: Metabolic
name: Hepatic steatosis
frequency: OCCASIONAL
description: >-
Hepatic steatosis can occur as part of the metabolic complication spectrum
of lipodystrophy.
phenotype_term:
preferred_term: Hepatic steatosis
term:
id: HP:0001397
label: Hepatic steatosis
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The metabolic abnormalities associated with lipodystrophy include insulin
resistance, hypertriglyceridemia, and hepatic steatosis.
explanation: >-
Lipodystrophy review evidence supports hepatic steatosis as a metabolic
complication in lipodystrophy syndromes.
biochemical:
- name: Low serum complement C3
presence: DECREASED
notes: >-
Low C3 is a central complement abnormality in BSS/APL and often occurs with
C3NeF-mediated alternative pathway activation.
biomarker_term:
preferred_term: Complement C3
term:
id: NCIT:C21527
label: Complement C3
readouts:
- target: Alternative Complement Pathway Dysregulation
relationship: READOUT_OF
direction: NEGATIVE
endpoint_context: DIAGNOSTIC
interpretation: Lower serum C3 reports alternative-complement consumption in BSS/APL.
evidence:
- reference: PMID:31924231
reference_title: Immunological features of patients affected by Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CONCLUSIONS: Our results confirmed the association between BSS,
autoimmunity and C3 hypocomplementemia.
explanation: >-
The cohort conclusion supports low C3 as a diagnostic readout of the
complement-dysregulated BSS/APL state.
evidence:
- reference: PMID:31924231
reference_title: Immunological features of patients affected by Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CONCLUSIONS: Our results confirmed the association between BSS,
autoimmunity and C3 hypocomplementemia.
explanation: >-
The immunology cohort directly supports low C3 as a BSS-associated
biochemical abnormality.
- name: C3 nephritic factor
presence: PRESENT
notes: >-
C3NeF positivity supports the diagnosis and provides a mechanistic clue for
chronic alternative pathway activation.
readouts:
- target: Alternative Complement Pathway Dysregulation
relationship: READOUT_OF
direction: PRESENT_ABSENT
endpoint_context: DIAGNOSTIC
interpretation: Presence of C3 nephritic factor supports C3 convertase-stabilizing alternative pathway dysregulation.
evidence:
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Laboratory findings such as low complement C3 and the presence of C3NeF
were used during the diagnosis of BSS.
explanation: >-
The factor D study supports C3NeF presence as a diagnostic marker of
BSS/APL complement dysregulation.
evidence:
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Laboratory findings such as low complement C3 and the presence of C3NeF
were used during the diagnosis of BSS.
explanation: >-
The factor D study describes low C3 and C3NeF as laboratory findings used
during BSS diagnosis.
- name: Complement factor D/adipsin
presence: INCREASED
notes: >-
Plasma factor D is elevated in BSS compared with comparator cohorts and may
function as a diagnostic biomarker.
biomarker_term:
preferred_term: Complement Factor D
term:
id: NCIT:C84326
label: Complement Factor D
readouts:
- target: Factor D/Adipsin Amplification in Adipose Tissue
relationship: READOUT_OF
direction: POSITIVE
endpoint_context: DIAGNOSTIC
interpretation: Elevated factor D/adipsin reports the adipose-linked alternative-complement amplification branch.
evidence:
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We found significantly elevated FD levels in BSS cases compared with the
remaining cohorts (p < 0.001).
explanation: >-
The case-control cohort supports elevated FD/adipsin as a readout of
the BSS/APL factor D branch.
evidence:
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We found significantly elevated FD levels in BSS cases compared with the
remaining cohorts (p < 0.001).
explanation: >-
Case-control data support elevated FD/adipsin in BSS.
- name: Blood triglyceride
presence: INCREASED
notes: >-
Increased circulating triglyceride is the measurable biochemical correlate
of hypertriglyceridemia when metabolic complications occur in partial
lipodystrophy.
biomarker_term:
preferred_term: triglyceride
term:
id: CHEBI:17855
label: triglyceride
readouts:
- target: Reduced adipose lipid-storage capacity
relationship: READOUT_OF
direction: POSITIVE
endpoint_context: MONITORING
interpretation: Higher blood triglyceride tracks the hypertriglyceridemia branch of reduced adipose lipid-storage capacity.
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The metabolic abnormalities associated with lipodystrophy include insulin
resistance, hypertriglyceridemia, and hepatic steatosis.
explanation: >-
Review evidence supports hypertriglyceridemia as a monitored metabolic
complication of lipodystrophy.
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The metabolic abnormalities associated with lipodystrophy include insulin
resistance, hypertriglyceridemia, and hepatic steatosis.
explanation: >-
This supports blood triglyceride as the laboratory correlate of the
hypertriglyceridemia complication.
histopathology:
- name: Atrophied adipocytes with macrophage-rich complement injury
diagnostic: false
description: >-
Affected adipose tissue can show adipocyte atrophy/death, abnormal
extracellular matrix, macrophage accumulation, and local complement
deposition.
evidence:
- reference: PMID:32890433
reference_title: "Evidence of ongoing complement activation on adipose tissue from an 11-year-old girl with Barraquer-Simons syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Adipose tissue from the patient showed atrophied and dead adipocytes, an
abnormal production of extracellular matrix, and a remarkable accumulation
of infiltrating CD68 macrophages and adipocyte precursors (marked by
c-Kit positiveness).
explanation: >-
Affected human adipose tissue showed adipocyte loss, matrix remodeling,
and macrophage-rich infiltration.
- reference: PMID:32890433
reference_title: "Evidence of ongoing complement activation on adipose tissue from an 11-year-old girl with Barraquer-Simons syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Simultaneous detection of IgG, C3, C5a and C5b-9 proved the ongoing
complement activity and complement-directed injury within the adipose
tissue.
explanation: >-
Immunostaining supported local complement-directed injury in affected
adipose tissue.
genetic:
- name: HLA-DRB1
gene_term:
preferred_term: HLA-DRB1
term:
id: hgnc:4948
label: HLA-DRB1
association: Risk-associated HLA allele enrichment, not a monogenic cause
notes: >-
Classic acquired partial lipodystrophy is not defined by causal monogenic
variants in the cited evidence. One immunology cohort found enrichment of
HLA-DRB1*11, especially DRB1*11:03, supporting immune-genetic
susceptibility rather than Mendelian inheritance.
evidence:
- reference: PMID:31924231
reference_title: Immunological features of patients affected by Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The HLA allele DRB1*11 was present in 54% of BSS patients, and the
majority of them (31%) were positive for *11:03 (vs 1.3% in the general
population).
explanation: >-
The cohort supports an HLA-DRB1 association signal but does not establish
a causal monogenic gene-disease relationship.
diagnosis:
- name: Clinical fat-distribution assessment
description: >-
Diagnosis begins with recognition of the characteristic acquired and
progressive upper-body fat-loss pattern with lower-extremity sparing.
diagnosis_term:
preferred_term: disease screening
term:
id: MAXO:0000124
label: disease screening
results: >-
Progressive loss of face, neck, upper-limb, thoracic, and abdominal
subcutaneous fat with lower-extremity sparing supports APL/BSS.
evidence:
- reference: PMID:32404319
reference_title: Lipotransfer provides effective soft tissue replacement for acquired partial lipodystrophy.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
It is a rare disease characterised by a gradual and progressive onset of
lipoatrophy limited to the face, neck, upper limbs, thorax and abdomen
and sparing the lower extremities.
explanation: >-
This case report supports the clinical fat-distribution pattern used for
recognition.
- name: Complement biomarker analysis
description: >-
Complement testing for C3, C4, C3NeF, factor B, and related complement
autoantibodies supports diagnosis and risk assessment.
diagnosis_term:
preferred_term: biomarker analysis
term:
id: MAXO:0000018
label: biomarker analysis
results: >-
Low complement C3 and C3NeF positivity support BSS/APL; elevated factor
D/adipsin may further support diagnosis in specialized settings.
evidence:
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Laboratory findings such as low complement C3 and the presence of C3NeF
were used during the diagnosis of BSS.
explanation: >-
The cohort methods describe low C3 and C3NeF as diagnostic laboratory
findings.
- reference: PMID:34205507
reference_title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Our results suggest that FD could be a reliable diagnostic biomarker
involved in the pathophysiology of BSS by promoting unrestrained local
complement system activation in the adipose tissue environment.
explanation: >-
The factor D study supports FD/adipsin as a candidate diagnostic
biomarker.
- name: Renal surveillance for complement-mediated glomerular disease
description: >-
Surveillance for renal involvement is important because C3 glomerulopathy
and membranoproliferative glomerulonephritis are mechanistically linked to
complement dysregulation and may present with proteinuria or kidney
dysfunction.
diagnosis_term:
preferred_term: disease screening
term:
id: MAXO:0000124
label: disease screening
results: >-
Proteinuria, hematuria, hypertension, kidney failure, or persistent low C3
should prompt evaluation for complement-mediated renal disease.
evidence:
- reference: PMID:38076230
reference_title: "C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The presenting features of these diseases are variable and may include
proteinuria, hematuria, hypertension, or kidney failure.
explanation: >-
C3 glomerulopathy review evidence supports renal surveillance endpoints.
- reference: PMID:38076230
reference_title: "C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
A common finding in these diseases is low serum C3 levels with normal
serum C4 levels.
explanation: >-
The review supports complement testing as part of renal evaluation.
- name: Metabolic complication surveillance
description: >-
Patients should be monitored for insulin resistance, hypertriglyceridemia,
and hepatic steatosis because acquired partial lipodystrophy is a
lipodystrophy syndrome with variable metabolic risk.
diagnosis_term:
preferred_term: disease screening
term:
id: MAXO:0000124
label: disease screening
results: >-
Abnormal fasting glucose/HbA1c, triglycerides, liver enzymes, or hepatic
imaging can identify metabolic complications requiring treatment.
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Lipodystrophies are heterogeneous disorders characterized by varying
degrees of body fat loss and predisposition to insulin resistance and its
metabolic complications.
explanation: >-
Review evidence supports monitoring for insulin-resistance complications
across lipodystrophy syndromes.
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The metabolic abnormalities associated with lipodystrophy include insulin
resistance, hypertriglyceridemia, and hepatic steatosis.
explanation: >-
The review specifies the metabolic complications to screen for.
treatments:
- name: Metabolic complication management
description: >-
Treatment of APL includes prevention and management of metabolic
complications such as insulin resistance, hypertriglyceridemia, and hepatic
steatosis when present.
treatment_term:
preferred_term: therapeutic procedure
term:
id: MAXO:0000002
label: therapeutic procedure
target_phenotypes:
- preferred_term: Insulin resistance
term:
id: HP:0000855
label: Insulin resistance
- preferred_term: Hypertriglyceridemia
term:
id: HP:0002155
label: Hypertriglyceridemia
- preferred_term: Hepatic steatosis
term:
id: HP:0001397
label: Hepatic steatosis
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Management focuses on preventing and treating metabolic complications.
explanation: >-
Review evidence supports metabolic prevention and treatment as the core
management principle for lipodystrophy syndromes.
target_mechanisms:
- target: Reduced adipose lipid-storage capacity
treatment_effect: MODULATES
description: >-
Management of metabolic complications acts downstream of reduced adipose
lipid-storage capacity to control insulin resistance, triglycerides, and
hepatic steatosis when present.
evidence:
- reference: PMID:27823605
reference_title: Lipodystrophy Syndromes.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Management focuses on preventing and treating metabolic complications.
explanation: >-
The review supports linking metabolic management to the metabolic
complication branch created by adipose fat loss.
- name: Metreleptin pharmacotherapy for severe metabolic complications
description: >-
Metreleptin is a recombinant leptin analogue with expanded-access evidence
in partial lipodystrophy patients with diabetes and/or hypertriglyceridemia.
Applicability to classic APL/BSS is limited because the Ajluni cohort was a
mixed partial-lipodystrophy cohort rather than APL-specific, and the
abstract states FDA approval for generalized forms of lipodystrophy.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: metreleptin
term:
id: NCIT:C170171
label: Metreleptin
target_phenotypes:
- preferred_term: Insulin resistance
term:
id: HP:0000855
label: Insulin resistance
- preferred_term: Hypertriglyceridemia
term:
id: HP:0002155
label: Hypertriglyceridemia
evidence:
- reference: PMID:27642538
reference_title: "Efficacy and Safety of Metreleptin in Patients with Partial Lipodystrophy: Lessons from an Expanded Access Program."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Metreleptin is approved by the United States Food and Drug Administration
for treatment of generalized forms of lipodystrophy.
explanation: >-
This establishes metreleptin's approved context and supports caution
when applying partial-lipodystrophy evidence to classic APL/BSS.
- reference: PMID:27642538
reference_title: "Efficacy and Safety of Metreleptin in Patients with Partial Lipodystrophy: Lessons from an Expanded Access Program."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Study FHA101 (ClinicalTrials.gov identifier: NCT00677313) was an
open-label, expanded-access, long-term clinical effectiveness and safety
study in 23 patients with partial lipodystrophy and diabetes and/or
hypertriglyceridemia with no prespecified leptin level.
explanation: >-
The expanded-access cohort directly studied metreleptin in partial
lipodystrophy with metabolic complications, but was not specific to
classic APL/BSS.
- reference: PMID:27642538
reference_title: "Efficacy and Safety of Metreleptin in Patients with Partial Lipodystrophy: Lessons from an Expanded Access Program."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
CONCLUSIONS: Our clinical observations document the large heterogeneity
and disease burden of partial lipodystrophy syndromes and suggest that
metreleptin treatment benefits may extend to patients with partial
lipodystrophy.
explanation: >-
The authors frame the benefit as potentially extending to partial
lipodystrophy, supporting limited rather than definitive applicability to
acquired partial lipodystrophy.
target_mechanisms:
- target: Reduced adipose lipid-storage capacity
treatment_effect: MODULATES
description: >-
Metreleptin is used for severe metabolic complications in
partial-lipodystrophy patients, acting on the downstream metabolic branch
rather than restoring lost adipose tissue.
evidence:
- reference: PMID:27642538
reference_title: "Efficacy and Safety of Metreleptin in Patients with Partial Lipodystrophy: Lessons from an Expanded Access Program."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Study FHA101 (ClinicalTrials.gov identifier: NCT00677313) was an
open-label, expanded-access, long-term clinical effectiveness and safety
study in 23 patients with partial lipodystrophy and diabetes and/or
hypertriglyceridemia with no prespecified leptin level.
explanation: >-
The expanded-access cohort supports a cautious mechanism link between
metreleptin and the metabolic-complication branch in partial
lipodystrophy.
- name: Autologous fat grafting or lipotransfer
description: >-
Autologous fat grafting/lipotransfer can be used for soft-tissue
restoration in disfiguring facial or upper-body lipoatrophy and has
published case-report support for quality-of-life benefit.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
target_phenotypes:
- preferred_term: Loss of facial adipose tissue
term:
id: HP:0000292
label: Loss of facial adipose tissue
- preferred_term: Lipoatrophy
term:
id: HP:0100578
label: Lipoatrophy
evidence:
- reference: PMID:27402657
reference_title: "Barraquer-Simons syndrome: a unique patient's perspective on diagnosis, disease progression and recontouring treatment."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Treatment of lipoatrophy in these patients is limited to cosmetic
restoration, and autologous fat grafting has shown sustained positive
effects with no or very little loss of volume at follow-ups.
explanation: >-
The patient-perspective case report supports autologous fat grafting for
lipoatrophy recontouring.
- reference: PMID:27402657
reference_title: "Barraquer-Simons syndrome: a unique patient's perspective on diagnosis, disease progression and recontouring treatment."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Furthermore, the treatment has resulted in considerable improvements in
her quality of life and daily functioning.
explanation: >-
The same report supports quality-of-life benefit after recontouring.
- reference: PMID:32404319
reference_title: Lipotransfer provides effective soft tissue replacement for acquired partial lipodystrophy.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Autologous fat transfer is an established plastic and reconstructive
procedure that is safe and minimally invasive and can be used to
reconstruct a variety of soft tissue defects and has shown to be an
effective treatment modality in patients with APL.
explanation: >-
A second case report supports lipotransfer as an effective reconstructive
treatment for APL soft-tissue defects.
- name: Hyaluronic acid filler for facial volume loss
description: >-
Hyaluronic acid filler can be used for midface volume restoration in
selected patients with BSS/APL.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: hyaluronic acid
term:
id: CHEBI:16336
label: hyaluronic acid
target_phenotypes:
- preferred_term: Loss of facial adipose tissue
term:
id: HP:0000292
label: Loss of facial adipose tissue
evidence:
- reference: PMID:30604443
reference_title: Hyaluronic acid fillers for correcting midface volume deficit in Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Fillers, autologous fat transplant or cosmetic surgeries can be used to
correct the volume deficit.
explanation: >-
The cosmetic dermatology case report identifies filler therapy as a
management option for volume deficit.
- reference: PMID:30604443
reference_title: Hyaluronic acid fillers for correcting midface volume deficit in Barraquer-Simons syndrome.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CONCLUSION: Hyaluronic acid filler is safe and effective for the
management of volume loss in BSS.
explanation: >-
The report supports hyaluronic acid filler for facial volume loss in BSS.
- name: Plastic surgeon evaluation
description: >-
Evaluation by plastic and reconstructive surgery is appropriate when
progressive lipoatrophy produces soft-tissue defects or psychosocial
burden requiring reconstructive planning.
treatment_term:
preferred_term: plastic surgeon evaluation
term:
id: MAXO:0000713
label: plastic surgeon evaluation
target_phenotypes:
- preferred_term: Lipoatrophy
term:
id: HP:0100578
label: Lipoatrophy
evidence:
- reference: PMID:32404319
reference_title: Lipotransfer provides effective soft tissue replacement for acquired partial lipodystrophy.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Treatment is aimed at surgical correction of soft tissue destruction.
explanation: >-
The case report supports surgical evaluation and reconstruction for
soft-tissue destruction.
clinical_trials:
- name: NCT06484868
phase: PHASE_IV
status: RECRUITING
description: >-
Open-label Phase IV post-authorisation trial evaluating daily subcutaneous
metreleptin treatment in people with partial lipodystrophy, including
acquired partial lipodystrophy in the Falcon report.
target_phenotypes:
- preferred_term: Insulin resistance
term:
id: HP:0000855
label: Insulin resistance
- preferred_term: Hypertriglyceridemia
term:
id: HP:0002155
label: Hypertriglyceridemia
evidence:
- reference: clinicaltrials:NCT06484868
reference_title: "A 24-Month, Multi-Centre, Open Label Phase IV Post Authorisation Efficacy Study to Evaluate the Efficacy, Safety and Immunogenicity of Daily Subcutaneous Metreleptin Treatment in Patients With Partial Lipodystrophy"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This is an Open Label, Phase IV, Post Authorisation Study to Evaluate the
Efficacy, Safety and Immunogenicity of Daily Subcutaneous Metreleptin
Treatment in people with Partial Lipodystrophy
explanation: >-
The ClinicalTrials.gov summary supports the Phase IV metreleptin study in
partial lipodystrophy. The structured status is recorded as recruiting.
references:
- reference: PMID:31924231
title: Immunological features of patients affected by Barraquer-Simons syndrome.
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
- reference: PMID:32890433
title: "Evidence of ongoing complement activation on adipose tissue from an 11-year-old girl with Barraquer-Simons syndrome."
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
- reference: PMID:34205507
title: Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
- reference: PMID:38678257
title: "Diagnostic and referral pathways in patients with rare lipodystrophy and insulin-resistance syndromes: key milestones assessed from a national reference center."
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
- reference: PMID:38076230
title: "C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis."
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
- reference: PMID:27823605
title: Lipodystrophy Syndromes.
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
- reference: PMID:18752661
title: "Impaired expression of mitochondrial and adipogenic genes in adipose tissue from a patient with acquired partial lipodystrophy (Barraquer-Simons syndrome): a case report."
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
- reference: PMID:27402657
title: "Barraquer-Simons syndrome: a unique patient's perspective on diagnosis, disease progression and recontouring treatment."
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
- reference: PMID:30604443
title: Hyaluronic acid fillers for correcting midface volume deficit in Barraquer-Simons syndrome.
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
- reference: PMID:32404319
title: Lipotransfer provides effective soft tissue replacement for acquired partial lipodystrophy.
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
- reference: PMID:27642538
title: "Efficacy and Safety of Metreleptin in Patients with Partial Lipodystrophy: Lessons from an Expanded Access Program."
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
- reference: clinicaltrials:NCT06484868
title: "A 24-Month, Multi-Centre, Open Label Phase IV Post Authorisation Efficacy Study to Evaluate the Efficacy, Safety and Immunogenicity of Daily Subcutaneous Metreleptin Treatment in Patients With Partial Lipodystrophy"
found_in:
- Acquired_Partial_Lipodystrophy-deep-research-falcon.md
notes: >-
Curation is based on the Falcon report and exact snippets from generated
reference caches. The cited evidence supports complement dysregulation and
immune-genetic susceptibility, but does not establish a monogenic cause for
classic acquired partial lipodystrophy.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on Acquired Partial Lipodystrophy covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.
For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.
Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed
Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Search first: CTD, PubMed, PheGenI, GxE databases
Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC
For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities
For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype
Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser
Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Search first: CDC databases, WHO, PubMed, NHANES
Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON
Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Search first: PubMed, Gene Ontology, Reactome
Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types
Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Search first: OMIM, Orphanet, HPO, PubMed
Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.
Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Search first: NSGC resources, ACMG guidelines, GeneReviews
Search first: Clinical guidelines, FDA approvals, PubMed
Search first: NCBI Taxonomy
Search first: VBO (Vertebrate Breed Ontology)
Search first: NCBI Gene
Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease
This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details
Acquired partial lipodystrophy (APL), classically termed Barraquer–Simons syndrome (BSS), is an ultra-rare acquired disorder characterized by progressive, usually symmetric cephalocaudal loss of subcutaneous adipose tissue (face → neck/shoulders/arms/trunk) with relative sparing of lower extremities (and sometimes relative lower-body fat hypertrophy) and a strong female predominance. (corvillo2020immunologicalfeaturesof pages 1-2, hussain2016lipodystrophysyndromes. pages 1-3, donadille2024diagnosticandreferral pages 4-6) A central current concept is that alternative complement pathway dysregulation—often with low serum C3 and C3 nephritic factor (C3NeF)—is mechanistically linked to adipocyte injury and to major complications such as membranoproliferative glomerulonephritis/C3 glomerulopathy. (corvillo2020immunologicalfeaturesof pages 1-2, corvillo2021complementfactord pages 1-2, corvillo2020evidenceofongoing pages 3-6)
BSS is an acquired form of partial lipodystrophy characterized by “bilateral symmetrical loss of adipose tissue that begins in the face and may variably spreads to neck, shoulders, arms and trunk, keeping intact the adipose tissue of the lower extremities.” (corvillo2020immunologicalfeaturesof pages 1-2)
The information in this report is derived from: (i) peer-reviewed cohort studies and case reports in humans, (ii) clinical registry/rare-disease referral pathway data, (iii) clinical trials registries for partial lipodystrophy/metreleptin, and (iv) mechanistic reviews integrating human and experimental data. (corvillo2020immunologicalfeaturesof pages 1-2, donadille2024diagnosticandreferral pages 4-6, corvillo2020evidenceofongoing pages 3-6, NCT06484868 chunk 1)
| Disease / preferred name | Definition / fat-loss pattern | Common synonyms | Key identifiers | Key laboratory hallmarks | Key comorbidities / associated findings | Key citation |
|---|---|---|---|---|---|---|
| Acquired Partial Lipodystrophy | Rare acquired partial lipodystrophy with gradual, usually symmetrical cephalocaudal loss of subcutaneous fat beginning in the face and extending to neck, shoulders, arms, trunk/upper body, with relative sparing of lower extremities and often relative lower-body fat accumulation (corvillo2020immunologicalfeaturesof pages 1-2, ceccarini2021autoimmunityinlipodystrophy pages 3-4, fossfreitas2025lipodystrophysyndromesone pages 10-11, hussain2016lipodystrophysyndromes. pages 1-3) | Barraquer–Simons syndrome; BSS; APL; progressive cephalothoracic lipodystrophy; cephalocaudal lipodystrophy (pliszka2025severeinsulinresistance pages 18-20, fossfreitas2025lipodystrophysyndromesone pages 10-11) | OMIM 608709 (reported in reviews) (pliszka2025severeinsulinresistance pages 18-20, fossfreitas2025lipodystrophysyndromesone pages 10-11) | Low serum C3 common; C3 nephritic factor (C3NeF) frequent; reductions in C4 and factor B also reported; other complement autoantibodies include anti-C3, anti-properdin, anti-factor B (corvillo2020immunologicalfeaturesof pages 1-2, ceccarini2021autoimmunityinlipodystrophy pages 3-4) | C3 glomerulopathy / membranoproliferative glomerulonephritis; autoimmune diseases; metabolic abnormalities can occur; retinal drusen reported in recent cohort work (corvillo2020immunologicalfeaturesof pages 1-2, pliszka2025severeinsulinresistance pages 18-20) | Corvillo F et al. Orphanet J Rare Dis 2020. DOI: 10.1186/s13023-019-1292-1 (corvillo2020immunologicalfeaturesof pages 1-2) |
| Complement-associated APL phenotype | Complement dysregulation–linked APL phenotype in which adipose tissue is a site of local alternative-pathway activation; adipocytes supply factor D/adipsin and may be selectively injured by complement activation products (corvillo2020evidenceofongoing pages 1-3, corvillo2021complementfactord pages 1-2) | Barraquer–Simons syndrome with complement dysregulation (corvillo2020evidenceofongoing pages 1-3, corvillo2021complementfactord pages 1-2) | No separate disease identifier established in gathered evidence | Persistent C3 hypocomplementemia; C3NeF-mediated stabilization of C3 convertase; elevated factor D/adipsin in plasma and atrophic adipose tissue; adipose deposition of IgG, C3, C5a, C5b-9/MAC in active lesions (corvillo2020evidenceofongoing pages 1-3, corvillo2020evidenceofongoing pages 3-6, corvillo2021complementfactord pages 1-2) | Progressive lipoatrophy; macrophage-rich inflammatory remodeling of adipose tissue; risk of later C3 glomerulopathy (corvillo2020evidenceofongoing pages 1-3, corvillo2021complementfactord pages 2-4) | Corvillo F et al. J Dermatol 2020. DOI: 10.1111/1346-8138.15570; Corvillo F et al. Int J Mol Sci 2021. DOI: 10.3390/ijms22126608 (corvillo2020evidenceofongoing pages 1-3, corvillo2021complementfactord pages 1-2) |
| Clinical recognition summary | Predominantly affects females, often begins in childhood/adolescence, and is frequently underrecognized with long referral/diagnostic delays in rare-disease pathways (corvillo2020immunologicalfeaturesof pages 1-2, donadille2024diagnosticandreferral pages 4-6, donadille2024diagnosticandreferral pages 2-4) | APL; BSS (donadille2024diagnosticandreferral pages 4-6, donadille2024diagnosticandreferral pages 2-4) | French rare-disease cohort recognized 33 APL/BSS cases among 292 analyzed lipodystrophy/insulin-resistance patients; no separate Orphanet code captured in gathered evidence (donadille2024diagnosticandreferral pages 4-6, donadille2024diagnosticandreferral pages 2-4) | Complement testing recommended in practice context because low C3 and/or C3NeF support diagnosis (donadille2024diagnosticandreferral pages 4-6, donadille2024diagnosticandreferral pages 2-4) | Renal disease association (MPGN/C3G), autoimmune overlap, and ocular drusen are clinically important complications to screen for (corvillo2020immunologicalfeaturesof pages 1-2, pliszka2025severeinsulinresistance pages 18-20) | Donadille B et al. Orphanet J Rare Dis 2024. DOI: 10.1186/s13023-024-03173-2 (donadille2024diagnosticandreferral pages 4-6, donadille2024diagnosticandreferral pages 2-4) |
Table: This table summarizes the core nomenclature and identifying features of acquired partial lipodystrophy/Barraquer–Simons syndrome, including its characteristic fat-loss pattern, synonyms, OMIM identifier, hallmark complement abnormalities, and major associated complications. It is useful as a compact reference for disease recognition and knowledge-base curation.
APL/BSS is generally considered acquired and frequently linked to immune/complement dysregulation, especially overactivation of the alternative complement pathway and autoantibodies that stabilize complement convertases. (corvillo2020immunologicalfeaturesof pages 1-2, corvillo2021complementfactord pages 1-2, corvillo2018acquiredpartiallipodystrophy pages 2-4)
Direct abstract support (immunology cohort): * “C3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features…” (corvillo2020immunologicalfeaturesof pages 1-2)
Demographic risk * Sex: females are more affected (reported ~4:1; cohort ratio 5.5:1 in one study; 90% female in a 2018–2023 French referral cohort’s APL group). (corvillo2020immunologicalfeaturesof pages 1-2, donadille2024diagnosticandreferral pages 4-6) * Age of onset: often childhood/adolescence (mean onset ~8 years in one cohort). (corvillo2020immunologicalfeaturesof pages 1-2)
Immune/complement risk and associated biology * C3NeF prevalence: 69.2% (9/13) in Corvillo et al. cohort; additional complement autoantibodies were frequent (anti-C3 38.5%; anti-properdin and anti-factor B 30.8% each). (corvillo2020immunologicalfeaturesof pages 1-2) * Complement factor D/adipsin (primarily synthesized by adipose tissue) is implicated because it activates the alternative pathway and may amplify local complement injury within adipose tissue. (corvillo2021complementfactord pages 1-2, corvillo2020evidenceofongoing pages 3-6)
Potential triggers * Viral infections are noted as preceding onset in some patients (reported in cohort background). (corvillo2020immunologicalfeaturesof pages 1-2)
No protective genetic or environmental factors were identified in the retrieved evidence.
Not directly established in the retrieved evidence; however, a plausible interaction is that environmental triggers (e.g., infections) may initiate or amplify autoimmune complement dysregulation in genetically susceptible backgrounds (e.g., HLA association signals). (corvillo2020immunologicalfeaturesof pages 1-2)
Metabolic disease is variable and often less frequent/severe than in generalized lipodystrophy, but can still be clinically significant. (corvillo2020immunologicalfeaturesof pages 1-2, oliveira2016barraquer–simonssyndromea pages 1-2) * In a 13-patient immunologic cohort: diabetes in 1 patient; elevated triglycerides/cholesterol in 2; fatty liver in 3. (corvillo2020immunologicalfeaturesof pages 1-2) * Case-based epidemiologic estimates summarized in Oliveira et al. (2016): diabetes ~10%, hypertriglyceridemia ~30%. (oliveira2016barraquer–simonssyndromea pages 1-2)
Renal disease is a major determinant of prognosis. * APL is described as associated with membranoproliferative glomerulonephritis in ~20% in one review/clinical classification source. (hussain2016lipodystrophysyndromes. pages 1-3) * Other summaries note one third with MPGN and that low C3/C3NeF may indicate renal involvement. (oliveira2016barraquer–simonssyndromea pages 1-2) * Complement cohort paper notes literature risk that ~20% of BSS patients eventually develop C3 glomerulopathy (C3G). (corvillo2020immunologicalfeaturesof pages 1-2)
Drusen may develop in complement-mediated renal disease contexts, and C3 glomerulopathy review notes that DDD patients may develop drusen and that DDD can be preceded/followed by APL. (ponticelli2023c3glomerulopathiesdense pages 1-2)
Autoimmune disease associations are common in some cohorts. * Corvillo et al.: autoimmune diseases in 38.5% (5/13). (corvillo2020immunologicalfeaturesof pages 1-2)
Facial/upper-body lipoatrophy can cause major psychosocial burden, and reconstructive procedures are implemented clinically to restore appearance. (jeon2020lipotransferprovideseffective pages 1-2)
A phenotype table with suggested HPO terms is provided below.
| Domain | Phenotype/complication | Frequency/statistic (with numerator/denominator if available) | Typical onset/progression notes | Suggested HPO terms |
|---|---|---|---|---|
| Body fat distribution | Symmetric cephalocaudal loss of subcutaneous fat affecting face, neck, shoulders, arms, trunk/upper thorax with sparing of lower extremities | Core defining phenotype; no pooled percentage given because it is used diagnostically (corvillo2020immunologicalfeaturesof pages 1-2, hussain2016lipodystrophysyndromes. pages 1-3, donadille2024diagnosticandreferral pages 4-6) | Usually begins in childhood or adolescence; gradual progressive spread from face downward over months to years; lower-body fat may become relatively increased after puberty, especially in females (corvillo2020immunologicalfeaturesof pages 1-2, hussain2016lipodystrophysyndromes. pages 1-3, oliveira2016barraquer–simonssyndromea pages 1-2) | HP:0001596 Lipodystrophy; HP:0001018 Facial hemiatrophy/facial lipoatrophy-like term not exact; HP:0010623 Abnormality of the neck; HP:0009125 Abnormal subcutaneous adipose tissue |
| Body fat distribution | Relative hypertrophy/increased fat in lower extremities or gluteofemoral region | Qualitative, reported in many women after puberty; no exact denominator in gathered cohort texts (corvillo2020immunologicalfeaturesof pages 1-2, oliveira2016barraquer–simonssyndromea pages 1-2) | Develops after upper-body fat loss; contributes to regional disproportion (corvillo2020immunologicalfeaturesof pages 1-2) | HP:0009125 Abnormal subcutaneous adipose tissue; HP:0012743 Abnormality of adipose tissue distribution |
| Body fat distribution | Female predominance | 90% women in French APL cohort (33 cases) (donadille2024diagnosticandreferral pages 4-6); literature female:male ratio about 4:1 (corvillo2020immunologicalfeaturesof pages 1-2, oliveira2016barraquer–simonssyndromea pages 1-2) | Sex bias apparent across cohorts; often recognized late despite childhood onset (donadille2024diagnosticandreferral pages 4-6, corvillo2020immunologicalfeaturesof pages 1-2) | HP:0011458 Abnormal sex ratio (disease-level descriptor; no exact patient HPO) |
| Metabolic | Diabetes mellitus / glucose intolerance | Diabetes about 10% in review/case-based overview (oliveira2016barraquer–simonssyndromea pages 1-2); one of 13 patients with diabetes in Corvillo cohort (1/13) (corvillo2020immunologicalfeaturesof pages 1-2) | Metabolic complications less common than in generalized or familial partial lipodystrophies, but can emerge with more extensive fat loss or longer disease duration (corvillo2020immunologicalfeaturesof pages 1-2, oliveira2016barraquer–simonssyndromea pages 1-2) | HP:0005978 Diabetes mellitus; HP:0003074 Hyperglycemia |
| Metabolic | Hypertriglyceridemia / dyslipidemia | Hypertriglyceridemia about 30% in review/case-based overview (oliveira2016barraquer–simonssyndromea pages 1-2); elevated TG in 2/13 in Corvillo cohort (corvillo2020immunologicalfeaturesof pages 1-2) | Often mild or absent early; should be monitored longitudinally because severity is variable (corvillo2020immunologicalfeaturesof pages 1-2, oliveira2016barraquer–simonssyndromea pages 1-2) | HP:0002155 Hypertriglyceridemia; HP:0003124 Hypercholesterolemia |
| Metabolic | Fatty liver / hepatic steatosis | 3/13 with fatty liver in immunologic cohort (corvillo2020immunologicalfeaturesof pages 1-2) | Can occur despite overall lower metabolic burden than other lipodystrophies; linked to ectopic fat and insulin resistance when present (corvillo2020immunologicalfeaturesof pages 1-2, hussain2016lipodystrophysyndromes. pages 1-3) | HP:0001397 Hepatic steatosis |
| Metabolic | Low/normal leptin, often less severe leptin deficiency than generalized lipodystrophy | Mild low leptin in 1/13 in Corvillo cohort (corvillo2020immunologicalfeaturesof pages 1-2) | Helps explain why metreleptin may be less effective in APL than in generalized lipodystrophy (oliveira2016barraquer–simonssyndromea pages 2-4) | HP:0012548 Abnormal circulating leptin level |
| Renal | Membranoproliferative glomerulonephritis / C3 glomerulopathy / dense deposit disease | ~20% develop MPGN in review (hussain2016lipodystrophysyndromes. pages 1-3); one third with MPGN in Oliveira overview (oliveira2016barraquer–simonssyndromea pages 1-2); 20–40% MPGN in later review (fossfreitas2025lipodystrophysyndromesone pages 10-11); 20% eventually develop C3G in immunology review (corvillo2020immunologicalfeaturesof pages 1-2); 3/13 had renal diagnoses in Corvillo cohort (DDD, IgA nephropathy, C3-related disease) (corvillo2020immunologicalfeaturesof pages 1-2) | Often occurs years after onset of fat loss; renal disease is the major prognostic determinant and may progress to ESRD (oliveira2016barraquer–simonssyndromea pages 1-2, corvillo2020immunologicalfeaturesof pages 1-2) | HP:0000093 Proteinuria; HP:0000083 Renal insufficiency; HP:0012590 Membranoproliferative glomerulonephritis; HP:0012584 C3 glomerulopathy |
| Renal | Low serum C3 associated with renal risk | Up to 80% with low serum C3 in review (fossfreitas2025lipodystrophysyndromesone pages 10-11); ~69% C3NeF positive and significant C3 reduction in 13-patient cohort (corvillo2020immunologicalfeaturesof pages 1-2) | Persistent hypocomplementemia may parallel disease activity and supports renal surveillance (corvillo2020immunologicalfeaturesof pages 1-2, oliveira2016barraquer–simonssyndromea pages 1-2) | HP:0012213 Decreased circulating complement C3 level |
| Ocular | Drusen / retinal deposits | Reported as a complication in DDD/APL overlap; no numerator in the specified evidence set here (ponticelli2023c3glomerulopathiesdense pages 1-2) | May occur in patients with complement-mediated disease, analogous to renal dense deposits (ponticelli2023c3glomerulopathiesdense pages 1-2) | HP:0000608 Retinal drusen |
| Autoimmune | Autoimmune disease association overall | 38.5% (5/13) in Corvillo cohort (corvillo2020immunologicalfeaturesof pages 1-2) | Autoimmune conditions may precede, accompany, or follow lipodystrophy; supports periodic autoimmune review of systems and serology as clinically indicated (corvillo2020immunologicalfeaturesof pages 1-2, oliveira2016barraquer–simonssyndromea pages 1-2) | HP:0002960 Autoimmunity |
| Autoimmune | Specific associated autoimmune conditions | Qualitative spectrum includes SLE, dermatomyositis, autoimmune thyroiditis, localized scleroderma, idiopathic thrombocytopenic purpura, Sjögren syndrome (corvillo2020immunologicalfeaturesof pages 1-2) | Association reinforces acquired/immune-mediated etiology in at least a subset of patients (corvillo2020immunologicalfeaturesof pages 1-2, donadille2024diagnosticandreferral pages 4-6) | HP:0002725 Systemic lupus erythematosus; HP:0003541 Dermatomyositis; HP:0000821 Hypothyroidism; HP:0002960 Autoimmunity |
| Diagnostic course / natural history | Childhood onset | Mean onset 8 years in Corvillo cohort (corvillo2020immunologicalfeaturesof pages 1-2); described as during childhood in review/classification texts (hussain2016lipodystrophysyndromes. pages 1-3, oliveira2016barraquer–simonssyndromea pages 1-2) | Insidious onset contributes to delayed diagnosis (donadille2024diagnosticandreferral pages 4-6) | HP:0011463 Childhood onset |
| Diagnostic course / natural history | Delayed recognition/referral | In French rare-disease cohort, APL median age at referral 42.3 years [IQR 28.7–58.8]; overall cohort diagnostic delay 6.4 years and referral delay 15.1 years (donadille2024diagnosticandreferral pages 4-6) | Suggests substantial under-recognition and need for earlier specialist referral (donadille2024diagnosticandreferral pages 4-6) | HP:0034198 Progressive course (disease-level descriptor) |
Table: This table summarizes the main clinical domains, complication frequencies, and onset/progression patterns reported for acquired partial lipodystrophy/Barraquer–Simons syndrome from the gathered evidence. It is useful for rapid knowledge-base curation and phenotype mapping with suggested HPO terms.
APL/BSS is typically acquired and not defined by single-gene causation in the retrieved primary evidence; however, immune-genetic associations have been reported. * HLA association signal: HLA DRB1*11 was present in 54% of BSS patients in one cohort (with enrichment of *11:03). (corvillo2020immunologicalfeaturesof pages 1-2)
No specific pathogenic germline variants were established as causal for classic acquired APL/BSS in the retrieved evidence.
Alternative complement pathway dysregulation → terminal complement activation → adipocyte injury is a leading mechanistic chain supported by human tissue evidence.
Key steps supported by retrieved evidence: 1. C3NeF stabilizes the alternative-pathway C3 convertase (C3bBb), preventing normal regulator-mediated decay and increasing C3 consumption and activation. (corvillo2020immunologicalfeaturesof pages 1-2, corvillo2018acquiredpartiallipodystrophy pages 2-4) 2. Adipose tissue produces complement components, especially factor D/adipsin, which is “a key activator of the AP,” making local adipose complement activation plausible. (corvillo2020evidenceofongoing pages 3-6, corvillo2021complementfactord pages 1-2) 3. In an 11-year-old with active disease, adipose tissue showed: atrophied/dead adipocytes, high extracellular matrix/fibrosis, increased CD68+ macrophages, recruitment of c-Kit+ adipocyte precursors, plus local complement deposition (C3, C5a, C5b-9) in affected tissue but not control tissue—supporting ongoing local complement-mediated injury. (corvillo2020evidenceofongoing pages 3-6) 4. The authors explicitly interpret colocalized C5a with macrophage crown-like structures as consistent with chemotaxis and inflammatory perpetuation. (corvillo2020evidenceofongoing pages 3-6)
Direct excerpted statements supporting local complement injury: * “C3 was detected…surrounding some adipocytes… C5a stained the CLS macrophages… C5b-9 was found ubiquitously…” (corvillo2020evidenceofongoing pages 3-6) * “This is the first report showing evidence of the activation of the complement system in affected subcutaneous WAT from a patient with BSS.” (corvillo2020evidenceofongoing pages 3-6)
Complement factor D/adipsin as a biomarker and potential amplifier * In Corvillo et al. 2021, FD was “significantly elevated” in BSS versus comparator cohorts and the authors conclude: “FD could be a reliable diagnostic biomarker…by promoting unrestrained local complement system activation in the adipose tissue environment.” (corvillo2021complementfactord pages 1-2)
GO biological processes (suggested) * complement activation, alternative pathway * regulation of complement activation * membrane attack complex assembly * macrophage chemotaxis * extracellular matrix organization / fibrosis
Cell Ontology (CL) (suggested) * macrophage (CD68+) * adipocyte * adipose stromal/progenitor cell (c-Kit+ precursors)
UBERON anatomical (suggested) * subcutaneous adipose tissue of face/neck/upper limb/trunk * kidney glomerulus * retina/macula (for drusen)
No specific toxic, occupational, lifestyle, or infectious agent has been established as causal; however, viral infections are described as preceding onset in some patients. (corvillo2020immunologicalfeaturesof pages 1-2) Lifestyle factors are relevant for management of metabolic complications but are not established as protective/causal in APL onset. (oliveira2016barraquer–simonssyndromea pages 2-4)
Upstream drivers: C3NeF and other complement autoantibodies (anti-C3, anti-properdin, anti-factor B) and reduced complement components (C3/C4/factor B) indicate complement dysregulation. (corvillo2020immunologicalfeaturesof pages 1-2)
Tissue-level effect: Local complement deposition and terminal pathway activation (C5b-9) are detected in affected subcutaneous adipose tissue during active disease, along with adipocyte death, macrophage infiltration, and fibrosis. (corvillo2020evidenceofongoing pages 3-6)
Downstream clinical manifestations: progressive lipoatrophy; risk of renal complement-mediated glomerular disease (C3G/DDD/MPGN) and occasional ocular drusen in complement-mediated contexts. (corvillo2020immunologicalfeaturesof pages 1-2, ponticelli2023c3glomerulopathiesdense pages 1-2)
Primary: subcutaneous adipose tissue (face, neck, upper limbs, upper trunk/thorax). (corvillo2020immunologicalfeaturesof pages 1-2, donadille2024diagnosticandreferral pages 4-6)
Secondary/complications * Kidney: glomerular disease including MPGN/C3G/DDD. (hussain2016lipodystrophysyndromes. pages 1-3, corvillo2020immunologicalfeaturesof pages 1-2) * Liver: fatty liver/steatosis in a subset. (corvillo2020immunologicalfeaturesof pages 1-2) * Eye: macular drusen in some complement-mediated cases. (ponticelli2023c3glomerulopathiesdense pages 1-2)
Prevalence/incidence estimates were not directly extractable from the retrieved texts; the disease is generally described via case counts. * Multiple sources report ~250 cases described in the literature. (pliszka2025severeinsulinresistance pages 17-18, oliveira2016barraquer–simonssyndromea pages 1-2)
APL/BSS is an acquired disorder and usually lacks family history. (corvillo2020immunologicalfeaturesof pages 1-2, corvillo2021complementfactord pages 1-2)
Diagnosis is primarily clinical based on characteristic fat-loss pattern, supported by complement and renal evaluation. (corvillo2020immunologicalfeaturesof pages 1-2, donadille2024diagnosticandreferral pages 4-6)
Key laboratory markers: * Complement C3: often low; persistent low C3 tracked with disease progression in an active pediatric case. (corvillo2020evidenceofongoing pages 3-6) * C3 nephritic factor (C3NeF): frequently present (e.g., 69.2% in one cohort). (corvillo2020immunologicalfeaturesof pages 1-2) * Complement factor D/adipsin (FD): elevated in BSS and proposed as a diagnostic biomarker. (corvillo2021complementfactord pages 1-2)
Example work-up elements reported in a clinical case-based overview include: CBC; renal/liver function tests; urinalysis and urinary albumin excretion; fasting glucose/insulin; HbA1c; OGTT; lipid profile; endocrine testing; and complement testing (C3, C4; C3NeF context). (oliveira2016barraquer–simonssyndromea pages 1-2)
Because renal prognosis is critical, renal screening/monitoring (renal function, urinalysis/albumin; nephrology referral) is emphasized in clinical descriptions and implemented in case management. (jeon2020lipotransferprovideseffective pages 1-2, oliveira2016barraquer–simonssyndromea pages 1-2)
In a rare-disease referral cohort, differential diagnoses (e.g., Cushing syndrome, acromegaly) were explicitly excluded as part of the diagnostic process for lipodystrophy/insulin-resistance presentations. (donadille2024diagnosticandreferral pages 2-4)
Treatment is individualized and typically targets (i) metabolic complications when present and (ii) disfiguring lipoatrophy.
Conventional approaches include diet/exercise, antihyperglycemics, and lipid-lowering therapy (general lipodystrophy management). (hussain2016lipodystrophysyndromes. pages 1-3, meehan2016metreleptinforinjection pages 1-3)
Evidence in partial lipodystrophy: In an expanded-access open-label study of 23 partial lipodystrophy patients, 1-year mean changes were HbA1c −0.88%, fasting glucose −42.0 mg/dL, triglycerides −119.8 mg/dL; common TEAEs included nausea 39.1%, hypoglycemia 26.1%, and UTI 26.1%, with no new immune-related safety signals. (ajluni2016efficacyandsafety pages 1-3) Regulatory context: Metreleptin is FDA-approved for generalized lipodystrophy (not partial), and expert summaries note less predictable efficacy in APL given less marked hypoleptinemia in many cases. (ajluni2016efficacyandsafety pages 1-3, oliveira2016barraquer–simonssyndromea pages 2-4)
Clinical-trial landscape (recent/active): * NCT06484868 (posted 2024-07-03; recruiting; Phase IV; open-label; n=12) explicitly includes confirmed familial or acquired partial lipodystrophy and uses HbA1c and triglyceride responder endpoints. (NCT06484868 chunk 1) * NCT05164341 (Phase III RCT; n=69) studies metreleptin in partial lipodystrophy but explicitly excludes acquired/radiation-induced partial lipodystrophy, limiting direct applicability to classic APL/BSS. (NCT05164341 chunk 1)
Autologous fat grafting (lipotransfer) is used to restore soft tissue in APL, especially facial lipoatrophy. * In a BMJ Case Report (published 2020-05), the patient underwent four procedures over 3 years, with average injected volume ~23 mL to the face per sitting and ~19 mL per breast in breast procedures; follow-up visits were arranged at 3–6 months and no major complications beyond minor donor-site bruising were reported. (jeon2020lipotransferprovideseffective pages 1-2)
A structured treatment table (with MAXO suggestions and key outcomes) is provided below.
| Intervention | Indication/target problem | Evidence type (trial/case report/review) | Key outcomes/stats | Safety notes | MAXO term suggestions | Citation |
|---|---|---|---|---|---|---|
| Diet and exercise / lifestyle modification | Baseline management of insulin resistance, dyslipidemia, hepatic steatosis, overall metabolic burden in APL/partial lipodystrophy | Review / case-based management summary | Recommended as foundational therapy; Oliveira et al. describe hypolipidic diet and regular exercise as part of APL management, especially when metabolic abnormalities are present or to reduce future risk; conventional therapy is often needed because metabolic burden is variable in APL (oliveira2016barraquer–simonssyndromea pages 2-4, hussain2016lipodystrophysyndromes. pages 1-3) | No disease-specific safety signal; effectiveness may be limited in severe metabolic disease | MAXO: dietary modification; exercise recommendation; metabolic disease management | (oliveira2016barraquer–simonssyndromea pages 2-4, hussain2016lipodystrophysyndromes. pages 1-3) |
| Conventional glucose-lowering therapy (e.g., metformin, insulin when needed) | Diabetes / severe insulin resistance in partial lipodystrophy | Review | Standard-of-care approach used before or alongside leptin therapy; partial lipodystrophy may require conventional antihyperglycemics, and severe cases may need high-dose insulin; benefit is supportive rather than disease-modifying (meehan2016metreleptinforinjection pages 1-3, hussain2016lipodystrophysyndromes. pages 1-3) | High insulin requirements may be needed in lipodystrophy; no APL-specific adverse-event profile reported in gathered evidence | MAXO: antihyperglycemic therapy; insulin therapy | (meehan2016metreleptinforinjection pages 1-3, hussain2016lipodystrophysyndromes. pages 1-3) |
| Lipid-lowering therapy (e.g., fibrates/statins/fish oil per standard practice) | Hypertriglyceridemia, dyslipidemia, pancreatitis risk reduction | Review / general management guidance | Used as part of conventional management for lipodystrophy-associated dyslipidemia; important because hypertriglyceridemia occurs in a subset of APL patients and may be difficult to normalize with standard therapy alone (hussain2016lipodystrophysyndromes. pages 1-3, meehan2016metreleptinforinjection pages 1-3) | Routine lipid-lowering drug safety considerations; no APL-specific signal in gathered evidence | MAXO: lipid-lowering therapy; hypertriglyceridemia management | (hussain2016lipodystrophysyndromes. pages 1-3, meehan2016metreleptinforinjection pages 1-3) |
| Thiazolidinediones (e.g., rosiglitazone/pioglitazone) | Insulin resistance and adipose redistribution in partial lipodystrophy | Review / case-based discussion | Reviews note thiazolidinediones have been used with good results in partial lipodystrophy; Oliveira et al. note rosiglitazone may increase fat in some affected areas but can worsen fat accumulation in unaffected areas, so use is individualized (meehan2016metreleptinforinjection pages 1-3, oliveira2016barraquer–simonssyndromea pages 2-4) | Potential to worsen regional fat distribution in APL; standard TZD adverse effects also apply | MAXO: thiazolidinedione therapy; insulin sensitizer therapy | (meehan2016metreleptinforinjection pages 1-3, oliveira2016barraquer–simonssyndromea pages 2-4) |
| Metreleptin in partial lipodystrophy (expanded access; not FDA-approved for PL/APL) | Diabetes, hypertriglyceridemia, leptin deficiency-related metabolic complications in partial lipodystrophy | Open-label expanded-access study (FHA101; NCT00677313) | In 23 PL patients, 1-year mean changes were HbA1c −0.88%, fasting glucose −42.0 mg/dL, triglycerides −119.8 mg/dL; larger effects in those with worse baseline abnormalities. Authors concluded benefits “may extend to patients with partial lipodystrophy,” but evidence remained preliminary (ajluni2016efficacyandsafety pages 1-3) | TEAEs mostly mild/moderate: nausea 39.1%, hypoglycemia 26.1%, urinary tract infections 26.1%; no new immune-related safety signals reported. Regulatory status: FDA approval is for generalized lipodystrophy, not PL/APL (ajluni2016efficacyandsafety pages 1-3) | MAXO: leptin replacement therapy; recombinant hormone therapy; subcutaneous drug administration | (ajluni2016efficacyandsafety pages 1-3) |
| Metreleptin in acquired partial lipoatrophy after transplantation / GVHD | Severe insulin resistance, hyperglycemia, hypertriglyceridemia in acquired partial lipoatrophy | Two case reports | In two adult acquired partial lipoatrophy cases, recombinant methionyl human leptin “reversed all of the metabolic abnormalities”; case 1 included TG 968 mg/dL, HbA1c 8.7%, GIR 2.32 mg/kg/min before therapy, with normalization of HbA1c and triglycerides reported after treatment (shibata2018acquiredpartiallipoatrophy pages 1-3) | Long-term treatment described as successful in these cases; detailed AE table not provided in extracted text | MAXO: leptin replacement therapy; insulin resistance treatment; hypertriglyceridemia treatment | (shibata2018acquiredpartiallipoatrophy pages 1-3) |
| Metreleptin for classic APL/BSS | Metabolic complications in APL/Barraquer–Simons syndrome | Review / expert commentary | Considered less predictably effective in classic APL because leptin levels are often relatively preserved compared with generalized lipodystrophy; Oliveira et al. specifically note lower efficacy in APL than in generalized forms (oliveira2016barraquer–simonssyndromea pages 2-4) | Use remains individualized and off-label in APL; benefit more likely when marked metabolic abnormalities/hypoleptinemia are present | MAXO: leptin replacement therapy | (oliveira2016barraquer–simonssyndromea pages 2-4) |
| Autologous fat grafting (lipotransfer) | Facial and breast lipoatrophy; psychosocial and cosmetic restoration | Single-patient real-world reconstructive case report | Four procedures over 3 years; mean injected volume about 23 mL to face per sitting and about 19 mL per breast in breast procedures. Report described effective soft-tissue replacement and real-world implementation for visible deformity (jeon2020lipotransferprovideseffective pages 1-2) | No major complications reported aside from minor donor-site bruising; follow-up scheduled at 3–6 months after procedures (jeon2020lipotransferprovideseffective pages 1-2) | MAXO: autologous fat grafting; reconstructive surgery; soft tissue augmentation | (jeon2020lipotransferprovideseffective pages 1-2) |
| Facial surgical correction / cosmetic reconstruction broadly | Disfiguring facial lipoatrophy and quality-of-life impact | Case report / review | Oliveira et al. emphasize surgical correction can successfully improve facial lipoatrophy and quality of life in APL, reflecting real-world practice when metabolic disease is absent or mild but deformity is substantial (oliveira2016barraquer–simonssyndromea pages 1-2, oliveira2016barraquer–simonssyndromea pages 2-4) | Standard surgical risks; no disease-specific complication pattern detailed in extracted evidence | MAXO: facial reconstructive surgery; cosmetic surgical procedure | (oliveira2016barraquer–simonssyndromea pages 1-2, oliveira2016barraquer–simonssyndromea pages 2-4) |
| Ongoing trial: metreleptin in partial lipodystrophy (NCT06484868) | Familial or acquired partial lipodystrophy with metabolic endpoints | Ongoing Phase IV open-label post-authorisation study | Recruiting; 24-month, single-group, estimated n=12; includes confirmed familial or acquired partial lipodystrophy. Primary endpoints at Month 12: proportion with ≥0.5% HbA1c reduction (or HbA1c <6.5%) and proportion with ≥30% TG reduction among those with severe baseline abnormalities (NCT06484868 chunk 1) | Safety endpoints include TEAEs, SAEs, deaths, AESIs, and discontinuations; no DMC listed in record (NCT06484868 chunk 1) | MAXO: leptin replacement therapy; clinical trial participation | (NCT06484868 chunk 1) |
| Ongoing trial: randomized metreleptin in PL (NCT05164341) | Partial lipodystrophy metabolic complications | Phase III randomized double-blind placebo-controlled trial | Actual enrollment 69; primary endpoints are change in HbA1c and percent change in fasting triglycerides at Month 6. Important limitation for APL knowledge base: this trial explicitly excludes acquired or radiation-induced partial lipodystrophy, so it does not directly study classic APL/BSS (NCT05164341 chunk 1, NCT05164341 chunk 2) | Quadruple masking; independent DMC; FDA-regulated drug study. Exclusion of acquired APL limits direct applicability to Barraquer–Simons syndrome (NCT05164341 chunk 1, NCT05164341 chunk 2) | MAXO: leptin replacement therapy; randomized controlled trial participation | (NCT05164341 chunk 1, NCT05164341 chunk 2) |
Table: This table summarizes treatment options and real-world implementations relevant to acquired partial lipodystrophy/Barraquer–Simons syndrome, including metabolic management, metreleptin evidence, reconstructive procedures, and ongoing trials. It is useful for quickly distinguishing what is standard practice, what is off-label or investigational, and which trial data are directly applicable to classic acquired APL.
No disease-specific primary prevention is established. Secondary/tertiary prevention focuses on: early recognition to reduce diagnostic delay and early screening for renal and metabolic complications. (donadille2024diagnosticandreferral pages 4-6, oliveira2016barraquer–simonssyndromea pages 1-2)
No naturally occurring APL/BSS analog in other species was identified in the retrieved evidence for this run.
No dedicated APL/BSS animal model evidence was retrieved in this run. Mechanistic reviews suggest broader experimental work on complement’s terminal cascade effects in adipose tissue (including the concept of complement-induced adipocyte autolysis), but this is not specific to a validated BSS model system in the evidence retrieved here. ()
The retrieved full texts in this run provided DOIs and journal metadata but not PMIDs for many citations; therefore, PMID identifiers cannot be reliably asserted from the available evidence without external database lookup.
References
(corvillo2020immunologicalfeaturesof pages 1-2): Fernando Corvillo, Giovanni Ceccarini, Pilar Nozal, Silvia Magno, Caterina Pelosini, Sofía Garrido, Alberto López-Lera, Manuela Moraru, Carlos Vilches, Silvia Fornaciari, Sabrina Gabbriellini, Ferruccio Santini, David Araújo-Vilar, and Margarita López-Trascasa. Immunological features of patients affected by barraquer-simons syndrome. Orphanet Journal of Rare Diseases, Jan 2020. URL: https://doi.org/10.1186/s13023-019-1292-1, doi:10.1186/s13023-019-1292-1. This article has 19 citations and is from a peer-reviewed journal.
(hussain2016lipodystrophysyndromes. pages 1-3): Iram Hussain and Abhimanyu Garg. Lipodystrophy syndromes. Endocrinology and metabolism clinics of North America, 45 4:783-797, Dec 2016. URL: https://doi.org/10.1016/j.ecl.2016.06.012, doi:10.1016/j.ecl.2016.06.012. This article has 240 citations and is from a peer-reviewed journal.
(donadille2024diagnosticandreferral pages 4-6): Bruno Donadille, Sonja Janmaat, Héléna Mosbah, Inès Belalem, Sophie Lamothe, Mariana Nedelcu, Anne-Sophie Jannot, Sophie Christin-Maitre, Bruno Fève, Camille Vatier, and Corinne Vigouroux. Diagnostic and referral pathways in patients with rare lipodystrophy and insulin-resistance syndromes: key milestones assessed from a national reference center. Orphanet Journal of Rare Diseases, 19:1-10, Apr 2024. URL: https://doi.org/10.1186/s13023-024-03173-2, doi:10.1186/s13023-024-03173-2. This article has 9 citations and is from a peer-reviewed journal.
(corvillo2021complementfactord pages 1-2): Fernando Corvillo, Laura González-Sánchez, Alberto López-Lera, Emilia Arjona, Giovanni Ceccarini, Ferruccio Santini, David Araújo-Vilar, Rebecca J Brown, Joan Villarroya, Francesc Villarroya, Santiago Rodríguez de Córdoba, Teresa Caballero, Pilar Nozal, and Margarita López-Trascasa. Complement factor d (adipsin) levels are elevated in acquired partial lipodystrophy (barraquer–simons syndrome). International Journal of Molecular Sciences, 22:6608, Jun 2021. URL: https://doi.org/10.3390/ijms22126608, doi:10.3390/ijms22126608. This article has 17 citations.
(corvillo2020evidenceofongoing pages 3-6): Fernando Corvillo, Pilar Nozal, Alberto López‐Lera, María P. De Miguel, Juan Alberto Piñero‐Fernández, Raúl De Lucas, María D García‐Concepción, María J. Beato, David Araújo‐Vilar, and Margarita López‐Trascasa. Evidence of ongoing complement activation on adipose tissue from an 11‐year‐old girl with barraquer–simons syndrome. The Journal of Dermatology, 47:1439-1444, Sep 2020. URL: https://doi.org/10.1111/1346-8138.15570, doi:10.1111/1346-8138.15570. This article has 6 citations.
(pliszka2025severeinsulinresistance pages 17-18): Monika Pliszka and Leszek Szablewski. Severe insulin resistance syndromes: clinical spectrum and management. International Journal of Molecular Sciences, 26:5669, Jun 2025. URL: https://doi.org/10.3390/ijms26125669, doi:10.3390/ijms26125669. This article has 13 citations.
(pliszka2025severeinsulinresistance pages 18-20): Monika Pliszka and Leszek Szablewski. Severe insulin resistance syndromes: clinical spectrum and management. International Journal of Molecular Sciences, 26:5669, Jun 2025. URL: https://doi.org/10.3390/ijms26125669, doi:10.3390/ijms26125669. This article has 13 citations.
(fossfreitas2025lipodystrophysyndromesone pages 10-11): Maria Foss-Freitas, Donatella Gilio, and Elif A. Oral. Lipodystrophy syndromes: one name but many diseases highlighting the importance of adipose tissue in metabolism. Current Diabetes Reports, Aug 2025. URL: https://doi.org/10.1007/s11892-025-01602-5, doi:10.1007/s11892-025-01602-5. This article has 5 citations and is from a peer-reviewed journal.
(NCT06484868 chunk 1): Open-label Study to Evaluate Metreleptin in Patients With Partial Lipodystrophy. Amryt Pharma. 2024. ClinicalTrials.gov Identifier: NCT06484868
(ceccarini2021autoimmunityinlipodystrophy pages 3-4): Giovanni Ceccarini, Silvia Magno, Donatella Gilio, Caterina Pelosini, and Ferruccio Santini. Autoimmunity in lipodystrophy syndromes. La Presse Médicale, 50:104073, Nov 2021. URL: https://doi.org/10.1016/j.lpm.2021.104073, doi:10.1016/j.lpm.2021.104073. This article has 37 citations.
(corvillo2020evidenceofongoing pages 1-3): Fernando Corvillo, Pilar Nozal, Alberto López‐Lera, María P. De Miguel, Juan Alberto Piñero‐Fernández, Raúl De Lucas, María D García‐Concepción, María J. Beato, David Araújo‐Vilar, and Margarita López‐Trascasa. Evidence of ongoing complement activation on adipose tissue from an 11‐year‐old girl with barraquer–simons syndrome. The Journal of Dermatology, 47:1439-1444, Sep 2020. URL: https://doi.org/10.1111/1346-8138.15570, doi:10.1111/1346-8138.15570. This article has 6 citations.
(corvillo2021complementfactord pages 2-4): Fernando Corvillo, Laura González-Sánchez, Alberto López-Lera, Emilia Arjona, Giovanni Ceccarini, Ferruccio Santini, David Araújo-Vilar, Rebecca J Brown, Joan Villarroya, Francesc Villarroya, Santiago Rodríguez de Córdoba, Teresa Caballero, Pilar Nozal, and Margarita López-Trascasa. Complement factor d (adipsin) levels are elevated in acquired partial lipodystrophy (barraquer–simons syndrome). International Journal of Molecular Sciences, 22:6608, Jun 2021. URL: https://doi.org/10.3390/ijms22126608, doi:10.3390/ijms22126608. This article has 17 citations.
(donadille2024diagnosticandreferral pages 2-4): Bruno Donadille, Sonja Janmaat, Héléna Mosbah, Inès Belalem, Sophie Lamothe, Mariana Nedelcu, Anne-Sophie Jannot, Sophie Christin-Maitre, Bruno Fève, Camille Vatier, and Corinne Vigouroux. Diagnostic and referral pathways in patients with rare lipodystrophy and insulin-resistance syndromes: key milestones assessed from a national reference center. Orphanet Journal of Rare Diseases, 19:1-10, Apr 2024. URL: https://doi.org/10.1186/s13023-024-03173-2, doi:10.1186/s13023-024-03173-2. This article has 9 citations and is from a peer-reviewed journal.
(corvillo2018acquiredpartiallipodystrophy pages 2-4): Fernando Corvillo and Margarita López-Trascasa. Acquired partial lipodystrophy and c3 glomerulopathy: dysregulation of the complement system as a common mechanism. Nefrologia, 38:258-266, May 2018. URL: https://doi.org/10.1016/j.nefroe.2018.04.002, doi:10.1016/j.nefroe.2018.04.002. This article has 21 citations and is from a peer-reviewed journal.
(oliveira2016barraquer–simonssyndromea pages 1-2): Joana Oliveira, Paula Freitas, Eva Lau, and Davide Carvalho. Barraquer–simons syndrome: a rare form of acquired lipodystrophy. BMC Research Notes, Mar 2016. URL: https://doi.org/10.1186/s13104-016-1975-9, doi:10.1186/s13104-016-1975-9. This article has 32 citations and is from a peer-reviewed journal.
(ponticelli2023c3glomerulopathiesdense pages 1-2): Claudio Ponticelli, Marta Calatroni, and Gabriella Moroni. C3 glomerulopathies: dense deposit disease and c3 glomerulonephritis. Frontiers in Medicine, Nov 2023. URL: https://doi.org/10.3389/fmed.2023.1289812, doi:10.3389/fmed.2023.1289812. This article has 19 citations.
(jeon2020lipotransferprovideseffective pages 1-2): Faith Hyun Kyung Jeon, Michelle Griffin, Carole Frosdick, and Peter Edward Michael Butler. Lipotransfer provides effective soft tissue replacement for acquired partial lipodystrophy. BMJ Case Reports, 13:e232601, May 2020. URL: https://doi.org/10.1136/bcr-2019-232601, doi:10.1136/bcr-2019-232601. This article has 4 citations and is from a peer-reviewed journal.
(oliveira2016barraquer–simonssyndromea pages 2-4): Joana Oliveira, Paula Freitas, Eva Lau, and Davide Carvalho. Barraquer–simons syndrome: a rare form of acquired lipodystrophy. BMC Research Notes, Mar 2016. URL: https://doi.org/10.1186/s13104-016-1975-9, doi:10.1186/s13104-016-1975-9. This article has 32 citations and is from a peer-reviewed journal.
(meehan2016metreleptinforinjection pages 1-3): Cristina Adelia Meehan, Elaine Cochran, Andrea Kassai, Rebecca J. Brown, and Phillip Gorden. Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. Expert Review of Clinical Pharmacology, 9:59-68, Jan 2016. URL: https://doi.org/10.1586/17512433.2016.1096772, doi:10.1586/17512433.2016.1096772. This article has 94 citations and is from a peer-reviewed journal.
(ajluni2016efficacyandsafety pages 1-3): Nevin Ajluni, M. Dar, John Xu, A. Neidert, and E. Oral. Efficacy and safety of metreleptin in patients with partial lipodystrophy: lessons from an expanded access program. Journal of diabetes & metabolism, Mar 2016. URL: https://doi.org/10.4172/2155-6156.1000659, doi:10.4172/2155-6156.1000659. This article has 62 citations.
(NCT05164341 chunk 1): Study to Evaluate the Safety and Efficacy of Daily Subcutaneous Metreleptin Treatment in Subjects With PL. Amryt Pharma. 2021. ClinicalTrials.gov Identifier: NCT05164341
(shibata2018acquiredpartiallipoatrophy pages 1-3): Yusuke Shibata, Atsuko Nakatsuka, Jun Eguchi, Satoshi Miyamoto, Yukari Masuda, Motoharu Awazawa, Akinobu Takaki, Ryuichi Yoshida, Takahito Yagi, and Jun Wada. Acquired partial lipoatrophy as graft-versus-host disease and treatment with metreleptin: two case reports. Journal of Medical Case Reports, Dec 2018. URL: https://doi.org/10.1186/s13256-018-1901-y, doi:10.1186/s13256-018-1901-y. This article has 13 citations and is from a peer-reviewed journal.
(NCT05164341 chunk 2): Study to Evaluate the Safety and Efficacy of Daily Subcutaneous Metreleptin Treatment in Subjects With PL. Amryt Pharma. 2021. ClinicalTrials.gov Identifier: NCT05164341