Lymphangioleiomyomatosis (LAM) is a rare systemic disease characterized by cystic lung destruction, renal angiomyolipomas (AMLs), and lymphangioleiomyomas. It is classified into tuberous sclerosis complex-associated LAM (TSC-LAM) and sporadic LAM based on the TSC mutations. We reported monozygotic twin sisters of TSC-LAM with sirolimus therapy for ten years. Both twins presented cystic lung involvement, renal AMLs, cerebral MRI alterations, and severe ventilatory impairment at baseline. During long-term treatment, lung function remained stable in both patients, although exercise capacity declined. Despite identical genetics, clinically relevant differences were observed: one twin exhibited earlier disease onset, irregular menstruation, higher VEGF-D and poorer exercise tolerance at baseline. During treatment, she experienced greater weight loss, fluctuating sirolimus concentrations, and earlier need for oxygen therapy. These findings highlight substantial phenotypic heterogeneity in TSC-LAM despite shared genetics and emphasize the importance of early diagnosis, individualized management, and therapeutic drug monitoring in this complex disease. • Early diagnosis of LAM is critical. Delayed recognition can lead to advanced lung impairment and limit treatment efficacy. • Phenotypic variability exists even in genetically identical LAM patients, highlighting the need for personalized management. • Low-dose sirolimus remains effective, and therapeutic drug monitoring can help reduce adverse effects by maintaining appropriate serum concentrations.
Fan et al. (Fri,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: