Clinical Features And Prognosis Of Methylmalonic Acidemia And Related Epilepsy

PARTⅠCLINICAL FEATURES OF EARLY-ONSET AND LATE-ONSET METHYLMALONIC ACIDEMIAObjective:To analyze and compare the clinical features of early-onset and late-onset methylmalonic acidemia(MMA).Methods:This study summarized the general data,clinical features,laboratory test,cerebrospinal fluid(CSF),electromyography(EMG),electroencephalography(EEG),cranial imaging and treatment regimen of 112 patients who were diagnosed as MMA at Qilu Hospital of Shandong University from January 2005 to December 2020,and compared the differences between early-onset and late-onset MMA.Results:1.The patients with late-onset MMA mainly showed neurological symptoms such as movement disorder,paresthesia and psychiatric symptoms.While the early-onset MMA patients had more variable symptoms,such as lethargy,poor feeding,et al.2.Early-onset patients were more likely to present with high lactic acid levels,increased blood ammonia,pancytopenia,liver damage,electrolyte disorder and myocardial damage.Patients with early-onset MMA had higher lactate and blood ammonia level than those with late-onset MMA.The majority of late onset MMA patients were combined with hyperhomocysteinemia.3.The main abnormality of EEG in patients with early-onset MMA was epileptiform discharges.Slow background rhythm was common in patients with late-onset MMA.Abnormal signals in brain parenchyma were significantly more common in patients with early-onset MMA,mostly in a symmetrical pattern.Foci of MMA can also be found in the spinal cord.4.In addition,the prognosis of early-onset MMA was worse.Conclusion:Patients with MMA had atypical clinical presentations,with a high mortality and disability rate,and were highly susceptible to misdiagnose.The clinical symptoms of patients with early-onset MMA were more severe than those with late-onset MMA,and the prognosis was worse.For suspected cases,blood tandem mass spectrometry(MS/MS),urine gas chromatography-mass spectrometry(GC-MS)and genetic test are required for early diagnosis and better prognosis.PART ⅡCLINICAL CHARACTERISTICS AND PROGNOSIS OF EPILEPSY IN METHYLMALONIC ACIDEMIAObjective:To summarize the clinical characteristics,treatment and prognosis of epilepsy in patients with methylmalonic acidemia(MMA).Methods:Patients with seizures were selected from those who attended Qilu Hospital of Shandong University and were diagnosed as MMA from January 2005 to December 2020.Their general information,seizure types,cranial imaging,electroencephalogram(EEG),treatment and outcome were reviewed.Results:1.MMA patients with epilepsy had an early onset.The type of seizures mainly included generalized tonic-clonic seizure and secondarily generalized epileptic seizure.2.Lactate level was higher in MMA Patients with seizures.While elevated blood ammonia was more common in patients without seizures.MMA Patients without seizures also had electroencephalographic changes such as slow background activity,extensive slow waves and even epileptiform discharges.3.Most MMA patients with seizures achieved complete remission after conventional MMA medication such as Vitamin B12,folic acid,betaine,L-carnitine and diet therapy.Antiepileptic drugs were required for patients with MMA who were at high risk of seizure recurrence.The use of levetiracetam was more frequent than other antiepileptic drugs.Conclusion:Conventional MMA medication could partially or even completely control seizures in MMA patients.Levetiracetam was preferred in clinical decision-making when choosing antiepileptic drugs.The exact effects of antiepileptic drugs on epilepsy associated with MMA still require further trials.