Late-onset severe axonal polyneuropathy in mut0 methylmalonic acidemia after liver-kidney transplantation: a genotype-informed case report

Background: Liver-kidney transplantation in methylmalonic acidemia (MMA) improves metabolic control but does not eliminate neurological risk. Peripheral neuropathy is increasingly recognized in transplanted patients, yet its pathophysiology and surveillance strategies remain poorly defined. Case presentation: We describe a severe axonal sensorimotor polyneuropathy that occurred 12 years after combined liver and kidney transplantation in a 20-year-old patient with mut0 methylmalonic acidemia (MMA), compound heterozygous for MMUT gene mutations and lacking fibroblast MCM enzymatic activity. Clinical, electrophysiological, and biochemical investigations were performed, including cerebrospinal fluid analysis, anti-ganglioside antibody testing, and measurement of circulating biomarkers of neuroaxonal injury (NfL) and mitochondrial dysfunction (FGF21, GDF15). Electrophysiological studies demonstrated a purely axonal process with active denervation. Cerebrospinal fluid protein and cell count were normal, anti-ganglioside antibodies were negative, and neuroimaging was unremarkable, excluding Guillain-Barré syndrome variants. Plasma NfL was markedly elevated (4083 pg/mL, 204× ULN), exceeding levels reported in hereditary and acquired neuropathies. FGF21 (1682 pg/mL) and GDF15 (1438 pg/mL) indicated mitochondrial stress. Conclusions: This case demonstrates that neurological stability is not guaranteed in mut0 MMA even 12 years post-transplantation. Management included switching from tacrolimus to everolimus and optimizing vitamin B12 supplementation. We propose NfL, FGF21, and GDF15 as monitoring tools for MMA transplant recipients.