Clinical heterogeneity and disease progression during adolescence in AGPAT2-associated congenital generalized lipodystrophy: a case series of four patients.
Jantje Weiskorn, Olga Kordonouri
✦ AI-curated · Sources linked
Case in brief
This case series followed four adolescents with genetically confirmed AGPAT2-associated congenital generalized lipodystrophy. All had generalized lipoatrophy, muscular hypertrophy, acromegaloid features, and hyperphagia, but metabolic severity varied, including between siblings with the same homozygous variant. The three female patients developed worsening insulin resistance, diabetes, and severe hypertriglyceridemia during puberty; the male remained relatively stable. Three developed progressive albuminuria, and two required ACE inhibitors for hypertension. Metreleptin improved metabolic measures and hyperphagia in treated patients, although illness-related decompensation occurred in one, and daytime fatigue persisted in three.
What made this case unusual
Marked clinical variability occurred despite the same genetic diagnosis, including discordant metabolic courses between siblings. Persistent daytime fatigue in three patients despite metabolic stabilization also suggested a possible disease component not captured by metabolic control alone.
Diagnostic / clinical pearl
In adolescent AGPAT2-associated CGL, monitor metabolic status closely through puberty and assess renal involvement, including albuminuria, even when diabetes is absent or controlled.
Why it matters
Metreleptin was associated with substantial metabolic improvement in treated patients, but acute illness could still precipitate decompensation and fatigue persisted in some, indicating that response may be incomplete.