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Course: Reversible Cortical and Basal Ganglia Lesions in Late-Onset Methylmalonic Aciduria

CME Credits: 1.00

Released: 2023-11-20

A 46-year-old man was admitted to the hospital due to acute-onset abdominal pain with vomiting and altered mental status after eating plenty of meat. His consciousness gradually deteriorated. His history included febrile seizures during infancy diagnosed as encephalitis, which were resolved after treatment, and delayed motor development since childhood. He denied any relevant family history and never drank alcohol. Physical examination revealed high-arched palate and prominent abdominal tenderness. Neurological examination found lethargy and hypomnesia, bilateral limb weakness, lower limb hypertonia, and bilateral positive Hoffmann and Babinski signs. Arterial blood gas revealed severe metabolic acidosis. Abdominal computed tomography with contrast confirmed acute pancreatitis. Brain magnetic resonance imaging indicated hyperintensities on T2-weighted fluid-attenuated inversion recovery imaging in bilateral temporal lobes, caudate nucleus head, and putamen without enhancement, and hyperintensities on diffusion-weighted imaging in bilateral temporal lobes (). The cerebrospinal fluid cell count and levels of protein, glucose, and chloride were normal, with results negative for oligoclonal bands and autoimmune encephalitis–related autoantibodies (anti–NMDA receptor, AMPA, ?-aminobutyric acid types A and B, voltage-gated potassium channel, DPPX, metabotropic glutamate receptor subtype 5, leucine-rich glioma inactivated 1, and contactin-associated protein-like 2) as well as anti-herpesviruses 1/2 IgG and IgM, and herpesvirus polymerase chain reaction. Therefore, viral and autoimmune encephalitis were excluded based on the investigation results. Meanwhile, posterior reversible encephalopathy syndrome was also excluded since the blood pressure was never elevated. Finally, cobalamin B (cblB)–type methylmalonic aciduria (MMA) was diagnosed by typical clinical manifestations, normal serum homocysteine level, and remarkably elevated levels of urine methylmalonic acid as well as plasma propionylcarnitine, together with an increased propionylcarnitine to acetylcarnitine ratio and homozygosity for a rare missense variant (c.646C>T; p.Leu216Phe; ) in the MMAB gene. Follow-up magnetic resonance imaging performed 10 days after treatment of intramuscular adenosylcobalamin and oral L-carnitine showed abnormal signals of basal ganglia and temporal lobes partially resolved both in diffusion-weighted imaging and T2 fluid-attenuated inversion recovery sequences (). During 1-year follow-up, the patient discontinued all drugs for 1 month, and test results showed normal serum vitamin B12 and homocysteine levels with significantly increased plasma propionylcarnitine and urine MMA levels, which further confirmed the diagnosis.


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