Overview
Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is a rare autosomal recessive disorder characterized by a near-complete absence of adipose (fat) tissue from birth or early infancy. The lack of functional fat tissue leads to severe metabolic complications because the body cannot properly store energy in fat cells. Instead, fat accumulates in organs such as the liver and muscles, causing significant health problems. There are four recognized subtypes (types 1–4) caused by mutations in different genes: AGPAT2 (type 1), BSCL2/seipin (type 2), CAV1 (type 3), and CAVIN1/PTRF (type 4), with types 1 and 2 being the most common. Patients typically present at birth or in the first year of life with a muscular appearance due to the near-total absence of subcutaneous fat. Key clinical features include severe insulin resistance, acanthosis nigricans (darkened, thickened skin patches), hypertriglyceridemia, hepatic steatosis (fatty liver) that can progress to cirrhosis, and diabetes mellitus that often develops during childhood or adolescence. Affected individuals may also have an increased appetite, accelerated linear growth, advanced bone age, and prominent muscularity. Women may develop polycystic ovary syndrome, hirsutism, and menstrual irregularities. Type 2 CGL is often associated with mild intellectual disability and a higher risk of cardiomyopathy. Hepatomegaly and splenomegaly are common findings. Management of CGL focuses on controlling the metabolic complications. Dietary management with a low-fat, high-complex-carbohydrate diet is a cornerstone of treatment. Metreleptin (recombinant human leptin) has been approved as a targeted therapy for the metabolic complications of generalized lipodystrophy, including CGL, and has shown significant benefits in improving insulin resistance, hypertriglyceridemia, and hepatic steatosis. Additional treatments may include insulin for diabetes, lipid-lowering agents, and management of organ-specific complications. Regular monitoring of liver function, cardiac status, and metabolic parameters is essential for long-term care.
Clinical phenotype terms— hover any for plain English:
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Neonatal
Begins at or shortly after birth (first 4 weeks)
FDA & Trial Timeline
2 eventsNovartis Pharmaceuticals
University of Liege — PHASE2
Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.
Treatments
1 availableMYALEPT
indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy
Clinical Trials
View all trials with filters →No actively recruiting trials found for Congenital generalized lipodystrophy at this time.
New trials open frequently. Follow this disease to get notified.
Rare Disease Specialist
Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Financial Resources
1 resourcesTravel Grants
No travel grants are currently matched to Congenital generalized lipodystrophy.
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Start the conversation →Latest news about Congenital generalized lipodystrophy
Disease timeline:
New recruiting trial: Allogeneic Hematopoietic Cell Transplantation From HLA-matched Donor After Flu-Mel-PTCy Versus Flu-Mel-ATG Reduced-intensity Conditioning
A new clinical trial is recruiting patients for Congenital generalized lipodystrophy
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Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Common questions about Congenital generalized lipodystrophy
What is Congenital generalized lipodystrophy?
Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is a rare autosomal recessive disorder characterized by a near-complete absence of adipose (fat) tissue from birth or early infancy. The lack of functional fat tissue leads to severe metabolic complications because the body cannot properly store energy in fat cells. Instead, fat accumulates in organs such as the liver and muscles, causing significant health problems. There are four recognized subtypes (types 1–4) caused by mutations in different genes: AGPAT2 (type 1), BSCL2/seipin (type 2), CAV1 (type 3), an
How is Congenital generalized lipodystrophy inherited?
Congenital generalized lipodystrophy follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does Congenital generalized lipodystrophy typically begin?
Typical onset of Congenital generalized lipodystrophy is neonatal. Age of onset can vary across affected individuals.
Which specialists treat Congenital generalized lipodystrophy?
25 specialists and care centers treating Congenital generalized lipodystrophy are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.