Clinical characteristics: Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.
Diagnosis/testing: The diagnosis of BSCL is established in a proband with three major criteria or two major criteria plus two or more minor criteria and/or by the identification of biallelic pathogenic variants in AGPAT2 or BSCL2.
Management: Treatment of manifestations: Restriction of total fat intake between 20% and 30% of total dietary energy maintains normal triglyceride serum concentration. Leptin therapy for treatment of hypertriglyceridemia and diabetes may be considered. Diabetes mellitus is managed as in childhood-onset diabetes mellitus.
Surveillance: Regular screening for glycosuria as a manifestation of diabetes mellitus, which usually starts in the teens (average age 12 years) but has also been described in infancy; monitoring for potential retinal, peripheral nerve, and renal complications of diabetes mellitus; yearly echocardiogram; yearly or biennial liver ultrasound examination to detect fatty infiltration.
Agents/circumstances to avoid: Excessive dietary fat intake.
Genetic counseling: BSCL is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family are known.
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