Аннотация
Abstract Introduction Familial partial lipodystrophy type 2 (FPLD2) is a rare autosomal dominant disorder caused by pathogenic LMNA variants. It is characterized by selective loss of subcutaneous fat, insulin resistance, dyslipidemia and hepatic steatosis. Cardiac involvement, including conduction defects and dilated cardiomyopathy (DCM), can be life-threatening. Clinical Case A 19-year-old girl presented with progressive cardiac dysfunction and a known diagnosis of LMNA-related FPLD2, confirmed at age 17 by a heterozygous pathogenic LMNA c.1488+1G>A variant (HGMD CS094346; PMIDs 20848652, 34240052). She had acanthosis nigricans, hirsutism, muscular extremities, and loss of subcutaneous fat from the face, abdomen, and limbs (BMI 14.06 kg/m²). At 16 years, she underwent ovarian cystectomy, and then she suffered an ischemic stroke affecting the left anterior and middle cerebral arteries. At 17 years, she developed hypertension and arrhythmias with alternating tachycardia and bradycardia. Echocardiography showed a dilated left ventricle, LVEF 14.3%, and mild pulmonary hypertension. NT-proBNP 276 pg/mL (N<125) indicated early cardiac damage, and an ICD was implanted. Metreleptin (0.4 mL s.c. daily) was started at the age of 18 years. Labs before therapy: fasting glucose 80.2 mg/dL (74-106), insulin 218 µIU/mL, HbA1c 6.2%, C-peptide 3.54 ng/mL (1.1-4.4); TG 1.56 mmol/L (0.44-1.4), LDL 0.67 mmol/L (0.91-1.91), low HDL; ALT 114.9 U/L, AST 93.9 U/L (N<35), indicating hepatic steatosis. Imaging revealed moderate hepatomegaly with diffuse hepatic steatosis and parenchymal changes in the pancreas and kidneys. After one year of therapy, metabolic parameters normalized: fasting glucose 98.1 mg/dL, HbA1c 5.7%, ALT 32.5 U/L, AST 39 U/L, TG 61.2 mg/dL, LDL 62.1 mg/dL. However, NT-proBNP increased to 4363 pg/mL (N<125), consistent with worsening heart failure. Despite therapy, she died approximately one year after treatment initiation due to complicated pneumonia and terminal cardiac failure. Discussion This case demonstrates a clear dissociation in LMNA-related FPLD2. Metreleptin reversed hepatic steatosis and normalized metabolic markers but failed to stop cardiomyopathy progression. This confirms that cardiac decline is driven by primary structural defects in the nuclear envelope rather than metabolic toxicity. The early stroke and multi-organ involvement underscore that LMNA-mutations are aggressive, systemic laminopathies. Ultimately, metabolic improvement provides a false sense of security; heart failure in these patients progresses independently of glycemic or lipid control, necessitating early and rigorous cardiac intervention. Conclusions Metreleptin improved hepatic and metabolic markers but failed to halt cardiac deterioration in LMNA-related FPLD2. Early recognition of cardiac manifestations and multidisciplinary follow-up are crucial to improving outcomes.