Clinical and electroencephalogram characteristics of methylmalonic acidemia with neurological injury

Abstract

Objective The study aims to investigate the clinical, imaging, and electroencephalogram (EEG) characteristics of methylmalonic academia (MMA) with nervous system damage as the primary manifestation.Methods From January 2017 to November 2022, patients with nervous system injury as the main clinical manifestation diagnosed as methylmalonic acidemia by hematuria metabolism or genetic test were collected and analyzed. Their clinical data, imaging data, and electroencephalogram data were analyzed.Result A total of 22 patients were enrolled, including 18 males and 4 females. The clinical symptoms included convulsions, developmental delay, feeding difficulties, poor feeding, disturbance of consciousness, abnormal movement (including involuntary movement, decreased muscle strength, and motor incoordination), and hypotonia. There were 8 cases (36%) of hydrocephalus, 2 cases (9%) of exencephaly effusion, 5 cases (22%) of corpus callosum dysplasia, 5 cases (22%) of myelination dysplasia, 1 case (4%) of abnormal frontal lobe signal, 1 case (4%) of decreased hippocampal volume, 6 cases (27%) of the abnormal lateral ventricular signal. Furthermore, 3 cases (13%) had abnormal signals in the basal ganglia. Also, there were 3 cases (13%) of cerebral atrophy/small parenchymal volume and 1 case (4%) of cytotoxic edema in the basal ganglia and cerebral peduncle. EEG data showed that there were 2 cases (9%) of hyper arrhythmia, 7 cases (31%) of voltage reduction, 13 cases (59%) of abnormal discharge, 15 cases (68%) of abnormal sleep physiological wave or abnormal sleep structure, 1 case (4%) of immature (delayed) EEG development, and 12 cases (54%) of slow background. There were 2 cases (9%) of spasms, 1 case (4%) of atonic seizures, and 1 case (4%) of myoclonic seizures. There were 20 patients (90%) with hyperhomocysteinemia. Treatments included intramuscular injections of vitamin B12, L-carnitine, betaine, folic acid, and oral therapy. Acute treatment included anti-infective, blood transfusion, gamma globulin, fluid replenishment, correcting acidosis, and other treatments. Other treatments include low protein diets, special formula milk powder, and antiepileptic treatment.Conclusion Methylmalonic acidemia can affect the central nervous system, leading to structural changes or abnormal signals in head MRI. Hematuric metabolic screening and genetic testing help make the diagnosis clear. EEG can reflect the changes in brain function in the acute phase. With the remission of the disease, the electroencephalogram can return to normal. However, the children may still experience some deterioration in development.