Long-term carglumic acid therapy in adult siblings with methylmalonic acidemia and advanced chronic kidney disease

Abstract

Abstract Background Evidence supporting long-term carglumic acid (CA) therapy in adult patients with methylmalonic acidemia (MMA), particularly those with advanced chronic kidney disease (CKD) or dialysis dependence, is extremely limited. Adult patients with MMA frequently experience recurrent metabolic decompensation and progressive multi-organ complications, for which effective chronic stabilization strategies are lacking. We describe the long-term clinical course of two adult siblings with MMA caused by pathogenic MMUT variants who were unresponsive to vitamin B12 therapy and developed advanced CKD. Both patients experienced frequent metabolic decompensation despite standard management. CA was initiated as adjunctive long-term therapy and patients were followed for up to 40 months. Results Following CA initiation, both siblings maintained stable plasma ammonia levels and had fewer metabolic decompensation episodes and hospitalizations. Improved dietary tolerance and daily functioning were also observed during follow-up. Longitudinal urinary methylmalonic acid levels fluctuated during treatment. No adverse events considered related to CA were observed in either patient during the treatment period. Conclusions These cases describe sustained clinical stability during long-term CA treatment in two adult siblings with MMA and advanced CKD, including dialysis dependence. CA may have a role as an adjunctive therapy during prolonged waiting periods prior to liver–kidney transplantation. Because of the case-based design and concomitant supportive treatments, further studies are needed to evaluate the potential role of long-term CA in this population.

The authors' abstract, as published at the source. Orphanet Journal of Rare Diseases, 2026 · DOI ↗