Congenital generalized lipodystrophy type 4

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ORPHA:228429OMIM:613327E88.1
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3Specialists8Treatment centers

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Overview

Congenital generalized lipodystrophy type 4 (CGL4), also known as Berardinelli-Seip congenital lipodystrophy type 4, is an extremely rare autosomal recessive disorder caused by mutations in the CAVIN1 gene (also known as PTRF, polymerase I and transcript release factor). This condition belongs to the group of congenital generalized lipodystrophies characterized by a near-complete absence of adipose (fat) tissue from birth or early infancy. The loss of fat tissue leads to a muscular appearance and is associated with severe metabolic complications including insulin resistance, diabetes mellitus, hypertriglyceridemia (high blood triglycerides), and hepatic steatosis (fatty liver). CGL4 is distinguished from other forms of congenital generalized lipodystrophy by the prominent involvement of skeletal muscle. Patients typically develop a progressive muscular dystrophy-like phenotype with elevated creatine kinase levels, muscle weakness, and cardiac abnormalities including hypertrophic cardiomyopathy and cardiac arrhythmias, which can be life-threatening. Additional features may include acanthosis nigricans (darkened, thickened skin patches), hepatomegaly (enlarged liver), and skeletal abnormalities such as atlantoaxial instability and joint contractures. Pyloric stenosis has also been reported in some affected individuals. There is currently no cure for CGL4. Management is primarily supportive and focuses on controlling metabolic complications through dietary modifications, including a low-fat diet, and pharmacological treatment of diabetes and dyslipidemia. Metreleptin (recombinant human leptin) therapy may be considered for managing metabolic abnormalities associated with leptin deficiency. Cardiac monitoring is essential due to the risk of arrhythmias and cardiomyopathy. A multidisciplinary approach involving endocrinologists, cardiologists, neurologists, and other specialists is recommended for comprehensive care.

Also known as:

Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Neonatal

Begins at or shortly after birth (first 4 weeks)

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Congenital generalized lipodystrophy type 4.

View clinical trials →

No actively recruiting trials found for Congenital generalized lipodystrophy type 4 at this time.

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Specialists

3 foundView all specialists →
LM
Leslie A Spikes, MD
KANSAS CITY, KS
Specialist
PI on 1 active trial1 Congenital generalized lipodystrophy type 4 publication
LM
Luigi R Boccardi, Ed.D., MPH
Specialist
PI on 1 active trial
LM
Lisa Mielniczuk, MD
ROCHESTER, MN
Specialist
PI on 1 active trial1 Congenital generalized lipodystrophy type 4 publication

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Congenital generalized lipodystrophy type 4.

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Common questions about Congenital generalized lipodystrophy type 4

What is Congenital generalized lipodystrophy type 4?

Congenital generalized lipodystrophy type 4 (CGL4), also known as Berardinelli-Seip congenital lipodystrophy type 4, is an extremely rare autosomal recessive disorder caused by mutations in the CAVIN1 gene (also known as PTRF, polymerase I and transcript release factor). This condition belongs to the group of congenital generalized lipodystrophies characterized by a near-complete absence of adipose (fat) tissue from birth or early infancy. The loss of fat tissue leads to a muscular appearance and is associated with severe metabolic complications including insulin resistance, diabetes mellitus,

How is Congenital generalized lipodystrophy type 4 inherited?

Congenital generalized lipodystrophy type 4 follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Congenital generalized lipodystrophy type 4 typically begin?

Typical onset of Congenital generalized lipodystrophy type 4 is neonatal. Age of onset can vary across affected individuals.

Which specialists treat Congenital generalized lipodystrophy type 4?

3 specialists and care centers treating Congenital generalized lipodystrophy type 4 are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.