20 Cases Of Inborn Errors Of Metabolism Presenting Epilepsy In Infants And Young Children

Objective:A retrospective analysis of 20 cases of epileptic seizures who had inborn errors of metabolism was made,including seizure form,accompanying manifestations before and during seizures,electroencephalogram,craniography,screening of tandem mass spectrometry(MS/MS)?gas chromatography-mass spectrometry(GC-MS)and gene sequence analysis,which could improve the understanding of this kind of disease.Methods: Collecting and analyzing the clinical data of infants presenting with seizures who were finally diagnosed as inborn errors of metabolism by tandem mass spectrometry?gas chromatography-mass spectrometry and gene sequence analysis in Affiliated Hospital of Qingdao University from February 2013 to May 2018.Results:(1)The study group included 20 children with inborn errors of metabolism presenting Epilepsy,including 10 cases of methylmalonic acidemia(10/20,50%),6 cases(6/10,60%)of isolated methylmalonic acidemia,4 cases(4/10,40%)of methylmalonic acidemia combined with homocystinemia;3(3/20,15%)cases of ornithine transcarbamylase deficiency(OTCD),2 cases(2/20,10%)of GM1 gangliosidosis,1 case(1/20,5%)of Leigh syndrome,1 case(1/20,5%)of glutaric acidemia type I(GA-I),1 case(1/20,5%)of pyridoxine-dependent epilepsy(PDE),1 case(1/20,5%)of adenylosuccinate lyase(ADSL)deficiency,1 case(1/20,5%)of biotinidase deficiency.(2)The age of onset of epilepsy was 1 day to 3 years old,the median age was 5 months old.8 cases(8/20,40%)of epilepsy occured in neonatal period(?28 days),including 6 cases(6/8,75%)of methylmalonic acidemia(MMA)(3 cases of isolated MMA and 3 cases of MMA combined with homocysteinemia),1 case of PDE(1/8,12.5%),1 case of ADSL deficiency(1/8,12.5%).4 cases(4/20,20%)occured in small infancy(>28 days to 6months),including 1 case of MMA,1 case of Leigh syndrome,1 case of GA-I,and 1 case of biotinidase deficiency.2 cases(2/20,10%)occured in infancy(7 months to 12 months),including 1 case of OTCD and 1 case of GM1 gangliosidosis.6 cases(6/20,30%)occured in early childhood(1-3 years old),including 3 cases of MMA,2 cases of OTCD,and 1 case of GM1 gangliosidosis.(3)Among the 20 children,11 cases(11/20,55%)were myoclonus,2 cases(2/20,10%)were convulsive epilepsy,and 2 cases(2/20,10%)were multiple type of seizures,2 cases(2/20,10%)were tonic-clonic seizure,2 cases(2/20,10%)were unable to classify,and 1cases(1/20,5%)were partial tetanus.(4)There were digestive symptoms(70% including feeding difficulties,low food intake,no weight gain or slow growth),mental and motor retardation(50%)or regression(20%)founded before seizures.(5)It can be accompanied by encephalopathy(65%)and other organ damage during seizures.This article collected 13 cases of encephalopathy(13/20,65%)(7 cases of MMA,3cases of OTCD,1 case of GM1 gangliosidosis,1 case of ADSL deficiency,1 case of Leigh syndrome).(6)There were 14 cases(14/20,70%)with EEG data,2 cases(14.3%)were normal,and the remaining(85.7%)EEG showed abnormal,including epileptic discharge,multifocal discharge,hypsarrhythmia and intermittent burst suppression.(7)There were 15 cases(15/20,75%)with cranial imaging data,3 cases(3/15,20%)showed no obvious abnormalities,and the remaining 12 cases(12/15,80%)had abnormal imaging data,including white matter lesions,ventricular system enlargement,brain atrophy,bilateral globus pallidus abnormalities,brain stem lesions,cerebral hemorrhage,cerebral infarction and other manifestations.(8)10 cases of MMA and 1 case of GA-I were diagnosed by MS/MS and GC-MS,three young children were suspected of OTCD by tandem mass spectrometry(MS/MS)and gas chromatography-mass spectrometry(GC-MS),who were final confirmed by gene sequence analysis.Two cases of GM1 gangliosidosis were diagnosed by ?-galactosidase activity of peripheral blood leukocytes.Leigh syndrome,ADSL deficiency,PDE and biotinidase deficiency were all diagnosed by gene sequence analysis.Conclusions:(1)Inborn errors of metabolism presenting Epilepsy often manifest myoclonic seizures and epileptic spasm.(2)Mental retardation and regression have occurred before seizures,and accompanied by feeding difficulties,less food intake,slow or no weight gain.(3)It can be accompanied by encephalopathy and other organ damage during seizures.(4)Cranial imaging often shows white matter lesions,brain atrophy,bilateral globus pallidus lesions and multiple lesions in brain stem.(5)These diseases can be diagnosed by MS/MS,GC-MS,detection of enzyme activity and gene sequence analysis.