Acute Neurological Complications After Transplantation in Methylmalonic Acidemia: A 35-Patient French Cohort.

Abstract

Transplantation is an effective therapeutic option to improve quality of life in patients with severe methylmalonic acidemia (MMA). However, data regarding neurological complications following transplantation remain limited. A retrospective, single-center study was conducted at Necker Hospital (France), including MMA patients who underwent kidney (KT), liver (LT), or liver-kidney transplantation (LKT) between 2007 and 2022. Our aim was to evaluate acute neurological complications occurring after transplantation, focusing on clinical features, laboratory parameters and neuroimaging. Sensorineural complications were also assessed. Thirty-five patients were included, 21 had undergone LKT, 10 LT and 4 KT. The median age at transplantation was 10.1 years, with a median follow-up of 5 years. Tacrolimus was used in 91% of patients. Acute neurological complications likely related to MMA occurred in 17% of patients. They include Leigh syndrome with identifiable triggers, observed in 4 patients (2 early and 2 late-post-transplantation), leading to one early- and one late-onset death. Stroke-like episodes occurred in 2 patients. Non-epileptic myoclonus, likely related to calcineurin inhibitor (CNI), were reported in 31% of patients. Pre-transplant brain MRI showed nonspecific abnormalities in 31% of patients and remained stable afterwards. Post-transplant ophthalmological data available for 17 patients showed 3 optic atrophies. No acute vision or hearing loss was reported. Although transplantation improves metabolic control in MMA, acute neurological complications can still occur following a triggering event, even years after transplantation. The risk may arise from sensitivity to CNI-induced neurotoxicity. Pre- and post-transplant neuroimaging, emergency metabolic protocols, and tailored immunosuppression are essential for long-term management.