Clinical Guidance

AGPAT2. No relationship appears to exist between the site and type of AGPAT2 pathogenic variants and severity of lipodystrophy or metabolic complications. BSCL2. With one exception (see following), no correlation between the site and type of a BSCL2 pathogenic variant and phenotype (including intellectual impairment) has been observed . Furthermore, related and unrelated individuals with the same pathogenic variant may be discordant for intellectual impairment. A severe form of BSCL characterized by lipodystrophy followed after a couple of months by neurologic regression and death has been described in five infants in Spain .

Source: GeneReviews — "Berardinelli-Seip Congenital Lipodystrophy"

Diagnostic Criteria

Suggestive Findings

Berardinelli-Seip congenital lipodystrophy (BSCL) should be suspected in individuals with one or more of the following major and/or minor findings.

Major Criteria

Lipoatrophy affecting the trunk, limbs, and face. Generalized lipodystrophy is apparent at birth. In some individuals, the face may be normal at birth with lipoatrophy becoming apparent during the first months of life. Lipoatrophy gives an athletic appearance, especially because skeletal muscle hypertrophy is also present. Acromegaloid features include gigantism, muscular hypertrophy, advanced bone age, prognathism, prominent orbital ridges, enlarged hands and feet, clitoromegaly, and enlarged external genitalia in males. Hepatomegaly.

Source: GeneReviews — "Berardinelli-Seip Congenital Lipodystrophy"

Differential Diagnosis

Congenital generalized lipodystrophy 3 (CGL3) (OMIM 612526). Individuals with this condition typically have serum creatine kinase concentrations between 2.5 and ten times the upper limit of normal in addition to features resembling classic BSCL . Two sibs of Hispanic ancestry with a homozygous CAV1 pathogenic missense variant and hypotonia, elevated serum creatine kinase, atlas-axis instability, and generalized lipodystrophy have been described . Congenital generalized lipodystrophy 4 (CGL4) (OMIM 613327).

Source: GeneReviews — "Berardinelli-Seip Congenital Lipodystrophy"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with Berardinelli-Seip congenital lipodystrophy (BSCL), the following clinical evaluations are recommended:

• Complete blood count

• Serum concentration of electrolytes, AST, alanine transaminase, urea, creatinine, insulin, C-peptide, triglycerides, and cholesterol

• Oral glucose tolerance test; when appropriate, clamp glucose homeostasis study

• Ultrasound of the liver to evaluate liver size and fatty content

• Echocardiogram to evaluate for cardiac hypertrophy

• Renal ultrasound examination to evaluate for kidney size

• Physical examination for orthopedic complications including reduced hip mobility and genu valgum

• Skeletal survey, especially of the long bones, to evaluate for bone cysts

• Bone age and assessment of sexual maturity rating/pubertal status

• Complete ophthalmologic examination, including slit lamp examination, to evaluate for ophthalmologic complications due to hyperlipemia and/or diabetes mellitus

• Assessment of cognitive ability with age-appropriate scales

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Restriction of total fat intake between 20% and 30% of total dietary energy is often sufficient to maintain normal triglyceride serum concentration. Fibric acid derivatives and n-3 polyunsaturated fatty acids derived from fish oils can be tried for the treatment of extreme hypertriglyceridemia.

Source: GeneReviews — "Berardinelli-Seip Congenital Lipodystrophy"

Clinical Guidance

Excessive dietary fat intake should be avoided.

Source: GeneReviews — "Berardinelli-Seip Congenital Lipodystrophy"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Berardinelli-Seip Congenital Lipodystrophy"

Surveillance Guidelines

The following are appropriate:

• Periodic screening for glycosuria as a manifestation of diabetes mellitus

• For individuals with diabetes mellitus, follow-up in a diabetes clinic every six months to monitor for possible retinal, peripheral nerve, and renal complications

• Yearly cardiac ultrasound and EKG

• Yearly or biennial liver ultrasound examination to detect fatty infiltration

Ultrasound surveillance is a noninvasive procedure that can, along with serum lipid concentrations and liver enzymes, provide information on the degree of lipid control and compliance with the fat-restricted diet.

Source: GeneReviews — "Berardinelli-Seip Congenital Lipodystrophy"